Sleep Apnea, ObstructivePhase 2/3NCT04394143
Effect of AD128 to Treat Obstructive Sleep Apnea
A Phase 2/3 study testing AD128 and Mannitol in people with Sleep Apnea, Obstructive, run by Raphael Heinzer at 1 site in Switzerland.
Trial summary
This study evaluates the combination of two drugs (AD128), to treat obstructive sleep apnea (OSA) severity. After a baseline evaluation and during 7 days, half of the participants will randomly receive this drug combination (AD128) and the other will receive a placebo, i.e. a drug without pharmaceutical effect. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- AD128 and Mannitol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 Oct 2020to 19 Jul 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (>18 years and ≤ 65 years)
- New or previous diagnosis of OSA with an AHI > 15/h on a polygraphic or polysomnographic recording (Participants already treated with continuous positive airway pressure (CPAP) or mandibular advancement device can be included but a 7-days wash-out period is required before the beginning of the protocol and CPAP usage will not be possible during the whole protocol duration),
- Informed Consent as documented by signature (Appendix Informed Consent Form)
Who cannot join
- History of seizures,
- History of glaucoma,
- History of benign prostatic hyperplasia, organic miction disorder or urinary retention,
- Gastrointestinal disease (e.g. stenosis, occlusion, ulcerative colitis, toxic megacolon, hiatal hernia…)
- Cardiac arrhythmia,
- History of bipolar disorder,
Show all 20Show fewer
- Use of respiratory stimulants or depressants,
- Use of Hypnotics,
- Use of Central nervous system stimulants,
- Use of Monoamine oxidase inhibitors (MAOIs) antidepressant,
- Major depressive disorder,
- Central sleep apnea representing more than 10% of all respiratory events
- Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
- Pregnant or breast feeding female participants or participants who intend to become pregnant during the study (However, there is no contraindication to contraception),
- Other clinically significant concomitant disease states (renal failure, hepatic dysfunction, severe cardiovascular or respiratory disease, myasthenia gravis, cerebral sclerosis),
- Known or suspected non-compliance, drug or alcohol abuse,
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
- Participation in another study with investigational drug within the 30 days preceding and during the present study
- Use or morphinic and derivatives which may influence sleep,
- Refusal to be informed in case of incidental findings.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of AD128 on Obstructive Sleep Apnea Severity: a Randomized, Placebo-controlled, Double-blind, Cross-over Study
This study evaluates the combination of two drugs (AD128), to treat obstructive sleep apnea (OSA) severity. After a baseline evaluation and during 7 days, half of the participants will randomly receive this drug combination (AD128) and the other will receive a placebo, i.e. a drug without pharmaceutical effect. Neither the participants, nor the investigators will know in which arm participants are until the end of the study. After one week of trial, an evaluation will be perform and will be follow by one week without any treatment. During the third and last week of trial, there will be a crossover of the groups, i.e. the participants of the first group who took the two drugs (AD128) during the first week will take a placebo and those who took the placebo will take the drugs combination.
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- AD128, Mannitol
- Keywords
- obstructive sleep apnea, pharmacologic treatment, sleepiness, vigilance
- Medical subject headings
- Sleep Apnea, Obstructive, Sleepiness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AD128Drug
Oral administration of two capsules before sleep for 7 days.
MannitolDrug
Also called Placebo
Oral administration of two capsules before sleep for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| AD128 | Experimental | The study specific intervention includes per oral administration of two capsules of AD128, once daily, just before lights out, for 7 days. Receives: Drug: AD128 |
| placebo | Placebo comparator | Two placebo capsules (Mannitol) will be administered for the control intervention once daily, just before light outs, for one week. Receives: Drug: Mannitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnea-hypopnea index (AHI)
Change from baseline AHI (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Secondary outcomes (25)
Oxygen desaturation index (ODI)
Change from baseline ODI (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Oxygen desaturation index (ODI) in REM and NREM
Change from baseline ODI (events/h) measured via polysomnography during rapid eye movement (REM) and non rapid eye movement (NREM) sleep between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Hypoxic load
Change from baseline hypoxic load (area under the curve of 3% oxygen desaturation related to apnea-hypopnea events) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Hypoxic load in REM and NREM
Change from baseline hypoxic load (area under the curve of 3% oxygen desaturation related to apnea-hypopnea events) measured via polysomnography during rapid eye movement (REM) and non rapid eye movement (NREM) sleep between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Arousal index
Change from baseline arousal index (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Arousal index in REM and NREM
Change from baseline arousal index (events/h) measured via polysomnography during rapid eye movement (REM) and non rapid eye movement (NREM) sleep between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Pulse wave amplitude (PWA) drops
Change from baseline PWA drops (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Pulse wave amplitude (PWA) drops in REM and NREM
Change from baseline PWA drops (events/h) measured via polysomnography during rapid eye movement (REM) and non rapid eye movement (NREM) sleep between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Apnea-hypopnea index (AHI) in REM and NREM
Change from baseline AHI (events/h) measured via polysomnography during rapid eye movement (REM) and non rapid eye movement (NREM) sleep between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of REM sleep
Change from baseline REM sleep (% of total sleep time) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of N1
Change from baseline sleep stage 1 (N1: % of total sleep time) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of N2
Change from baseline sleep stage 2 (N2: % of total sleep time) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of N3
Change from baseline sleep stage 3 (N3: % of total sleep time) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of alpha wave
Change from baseline alpha wave frequency (8-13 Hz - % of total sleep time) measured via polysomnography in REM and NREM between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of beta wave
Change from baseline beta wave frequency (13-30 Hz - % of total sleep time) measured via polysomnography in REM and NREM between the week of investigational treatment (AD-128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of gamma wave
Change from baseline gamma wave frequency (30-100 Hz - % of total sleep time) measured via polysomnography in REM and NREM between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of theta wave
Change from baseline theta wave frequency (4-8 Hz - % of total sleep time) measured via polysomnography in REM and NREM between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Percentage of delta wave
Change from baseline delta wave frequency (1-4 Hz - % of total sleep time) measured via polysomnography in REM and NREM between the week of investigational treatment (AD128) and the week of placebo treatment.
Measured: Day 7 and 21
Reaction time PVT
Change from baseline reaction time (in ms) during Psychomotor Vigilance Task (PVT). During 10 min, subjects were instructed to press a button as quickly as possible when a red millisecond-counter appeared on a small screen (PVT-192, Ambulatory Monitoring Inc.).
Measured: Day 7 and 21
Lapse PVT
Change from baseline lapse time (in ms) during Psychomotor Vigilance Task (PVT) and defined as reaction time > 500 ms). During 10 min, subjects were instructed to press a button as quickly as possible when a red millisecond-counter appeared on a small screen (PVT-192, Ambulatory Monitoring Inc.).
Measured: Day 7 and 21
Chronic Excessive daytime sleepiness (EDS)
Change from baseline Epworth Sleepiness Scale (ESS) score between the week of investigational treatment (AD128) and the week of placebo treatment.
The ESS is a 8-item questionnaire. ESS score can range from 0 to 24. The higher the ESS score, the higher daytime sleepiness.
Measured: Day 7 and 21
Acute Excessive daytime sleepiness (EDS)
Change from baseline Stanford Sleepiness Scale (SSS) score between the week of investigational treatment (AD128) and the week of placebo treatment.
Consisting of only one item, the scale requires respondents to select one of seven statements best representing their level of perceived sleepiness. The scale range from 1 to 7. Higher score indicates greater sleepiness.
Measured: Day 7 and 21
Sleep quality
Change from baseline visual analogic scale (VAS) sleep quality score between the week of investigational treatment (AD128) and the week of placebo treatment. Score ranges from 0 to 10. Higher score indicates better sleep quality.
Measured: Day 7 and 21
Fatigue
Change from baseline Pichot scale score between the week of investigational treatment (AD128) and the week of placebo treatment.
The Pichot scale is a 8-items auto-questionnaire to assess excessive fatigue. Score varies between 0 and 32, a score > 22 indicates excessive fatigue.
Measured: Day 7 and 21
Systolic and diastolic blood pressure
Change from baseline office systolic and diastolic blood pressure (BP in mm Hg) between the week of investigational treatment (AD128) and the week of placebo treatment.
The Pichot scale is a 8-items auto-questionnaire to assess excessive fatigue. Score varies between 0 and 32, a score > 22 indicates excessive fatigue.
Measured: Day 7 and 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start20 Oct 2020
- Primary completion19 Jul 2021
- Study completion19 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep Apnea, ObstructiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a randomized, placebo-controlled, double-blind crossover study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Raphael Heinzer
- Sponsor type
- University, hospital or other
- Collaborators
- Apnimed
- Responsible party
- Sponsor-investigator, Raphael Heinzer, Centre Hospitalier Universitaire Vaudois
- Investigators
- Raphael Heinzer, MD, Principal investigator, University Hospital of Lausanne (CHUV)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04394143
- Sponsor's protocol ID
- 2020-00315
- Status last verified
- Aug 2021
- First submitted
- 11 May 2020
- Last updated
- 6 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) could be transmitted on request after publication to researchers who provide a methodologically sound proposal.
Publications
Berger M, Solelhac G, Marchi NA, Dussez R, Bradley B, Lecciso G, Heiniger G, Bayon V, Van Den Broecke S, Haba-Rubio J, Siclari F, Heinzer R. Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial. Sleep. 2023 Jul 11;46(7):zsad051. doi: 10.1093/sleep/zsad051.
PubMed 36861433
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of AD128 on Obstructive Sleep Apnea Severity: a Randomized, Placebo-controlled, Double-blind, Cross-over Study
- ClinicalTrials.gov ID
- NCT04394143
- Acronym / sponsor ID
- 2020-00315
- Conditions
- Sleep Apnea, Obstructive
- Keywords
- obstructive sleep apnea, pharmacologic treatment, sleepiness, vigilance
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Raphael HeinzerUniversity, hospital or other
- Collaborators
- Apnimed
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- 19 Jul 2021 (actual)
- Study completion
- 19 Jul 2021 (actual)
- First posted
- 19 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the combination of two drugs (AD128), to treat obstructive sleep apnea (OSA) severity. After a baseline evaluation and during 7 days, half of the participants will randomly receive this drug combination (AD128) and the other will receive a placebo, i.e. a drug without pharmaceutical effect. Neither the participants, nor the investigators will know in which arm participants are until the end of the study. After one week of trial, an evaluation will be perform and will be follow by one week without any treatment. During the third and last week of trial, there will be a crossover of the groups, i.e. the participants of the first group who took the two drugs (AD128) during the first week will take a placebo and those who took the placebo will take the drugs combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized, placebo-controlled, double-blind crossover study
| Arm | Type | Receives |
|---|---|---|
| AD128 | Experimental | Drug: AD128The study specific intervention includes per oral administration of two capsules of AD128, once daily, just before lights out, for 7 days. |
| placebo | Placebo comparator | Drug: MannitolTwo placebo capsules (Mannitol) will be administered for the control intervention once daily, just before light outs, for one week. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults (>18 years and ≤ 65 years)
- New or previous diagnosis of OSA with an AHI > 15/h on a polygraphic or polysomnographic recording (Participants already treated with continuous positive airway pressure (CPAP) or mandibular advancement device can be included but a 7-days wash-out period is required before the beginning of the protocol and CPAP usage will not be possible during the whole protocol duration),
- Informed Consent as documented by signature (Appendix Informed Consent Form)
Key exclusion criteria (20 listed)
- History of seizures,
- History of glaucoma,
- History of benign prostatic hyperplasia, organic miction disorder or urinary retention,
- Gastrointestinal disease (e.g. stenosis, occlusion, ulcerative colitis, toxic megacolon, hiatal hernia…)
- Cardiac arrhythmia,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AD128Oral administration of two capsules before sleep for 7 days. | Drug | AD128 |
| MannitolAlso: PlaceboOral administration of two capsules before sleep for 7 days. | Drug | placebo |
Primary outcome
Apnea-hypopnea index (AHI)
Time frame: Day 7 and 21
Change from baseline AHI (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.
25 secondary outcomes
Oxygen desaturation index (ODI)
Time frame: Day 7 and 21
Oxygen desaturation index (ODI) in REM and NREM
Time frame: Day 7 and 21
Hypoxic load
Time frame: Day 7 and 21
Hypoxic load in REM and NREM
Time frame: Day 7 and 21
Arousal index
Time frame: Day 7 and 21
Arousal index in REM and NREM
Time frame: Day 7 and 21
Pulse wave amplitude (PWA) drops
Time frame: Day 7 and 21
Pulse wave amplitude (PWA) drops in REM and NREM
Time frame: Day 7 and 21
Apnea-hypopnea index (AHI) in REM and NREM
Time frame: Day 7 and 21
Percentage of REM sleep
Time frame: Day 7 and 21
Percentage of N1
Time frame: Day 7 and 21
Percentage of N2
Time frame: Day 7 and 21
Percentage of N3
Time frame: Day 7 and 21
Percentage of alpha wave
Time frame: Day 7 and 21
Percentage of beta wave
Time frame: Day 7 and 21
Percentage of gamma wave
Time frame: Day 7 and 21
Percentage of theta wave
Time frame: Day 7 and 21
Percentage of delta wave
Time frame: Day 7 and 21
Reaction time PVT
Time frame: Day 7 and 21
Lapse PVT
Time frame: Day 7 and 21
Chronic Excessive daytime sleepiness (EDS)
Time frame: Day 7 and 21
Acute Excessive daytime sleepiness (EDS)
Time frame: Day 7 and 21
Sleep quality
Time frame: Day 7 and 21
Fatigue
Time frame: Day 7 and 21
Systolic and diastolic blood pressure
Time frame: Day 7 and 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2021.
- Derived from this study: PubMed 36861433Berger M, Solelhac G, Marchi NA, Dussez R, Bradley B, Lecciso G, Heiniger G, Bayon V, Van Den Broecke S, Haba-Rubio J, Siclari F, Heinzer R. Effect of oxybutynin and reboxetine on obstructive sleep apnea: a randomized, placebo-controlled, double-blind, crossover trial. Sleep. 2023 Jul 11;46(7):zsad051. doi: 10.1093/sleep/zsad051.
- Individual participant dataSharing planned: No. Individual participant data (IPD) could be transmitted on request after publication to researchers who provide a methodologically sound proposal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raphael Heinzer, MD principal investigator
University Hospital of Lausanne (CHUV)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AD128 and Mannitol in people with Sleep Apnea, Obstructive, run by Raphael Heinzer at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apnea-hypopnea index (AHI) (time frame: Day 7 and 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04394143, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2021.