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Effect of AD128 to Treat Obstructive Sleep Apnea

Primary Purpose

Sleep Apnea, Obstructive

Status

Completed

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

AD128

Mannitol

About this trial

This is an interventional treatment trial for Sleep Apnea, Obstructive focused on measuring obstructive sleep apnea, pharmacologic treatment, sleepiness, vigilance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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,
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.

Sites / Locations

Centre Hospitalier Universitaire Vaudois

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AD128

placebo

Arm Description

The study specific intervention includes per oral administration of two capsules of AD128, once daily, just before lights out, for 7 days.

Two placebo capsules (Mannitol) will be administered for the control intervention once daily, just before light outs, for one week.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.).

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.).

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04394143

First Posted

May 11, 2020

Last Updated

August 5, 2021

Sponsor

Raphael Heinzer

Collaborators

Apnimed

1. Study Identification

Unique Protocol Identification Number

NCT04394143

Brief Title

Effect of AD128 to Treat Obstructive Sleep Apnea

Official Title

Effect of AD128 on Obstructive Sleep Apnea Severity: a Randomized, Placebo-controlled, Double-blind, Cross-over Study

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

October 20, 2020 (Actual)

Primary Completion Date

July 19, 2021 (Actual)

Study Completion Date

July 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Raphael Heinzer

Collaborators

Apnimed

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sleep Apnea, Obstructive

Keywords

obstructive sleep apnea, pharmacologic treatment, sleepiness, vigilance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Model Description

This is a randomized, placebo-controlled, double-blind crossover study

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Evaluators, investigators and patients will be blinded to treatment allocation. Treatments will be prepared and conditioned by the Pharmacy Service of the University Hospital of Lausanne according to a randomisation list performed by an independent statistician. The Pharmacy service is completely independent from the Center for Investigation and Research in Sleep (CIRS). Unblinding will be performed after statistical analysis is completed by a statistician blinded to treatment assignment.

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AD128

Arm Type

Experimental

Arm Description

The study specific intervention includes per oral administration of two capsules of AD128, once daily, just before lights out, for 7 days.

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Two placebo capsules (Mannitol) will be administered for the control intervention once daily, just before light outs, for one week.

Intervention Type

Drug

Intervention Name(s)

AD128

Intervention Description

Oral administration of two capsules before sleep for 7 days.

Intervention Type

Drug

Intervention Name(s)

Mannitol

Other Intervention Name(s)

Placebo

Intervention Description

Oral administration of two capsules before sleep for 7 days.

Primary Outcome Measure Information:

Title

Apnea-hypopnea index (AHI)

Description

Change from baseline AHI (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.

Time Frame

Day 7 and 21

Secondary Outcome Measure Information:

Title

Oxygen desaturation index (ODI)

Description

Change from baseline ODI (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.

Time Frame

Day 7 and 21

Title

Oxygen desaturation index (ODI) in REM and NREM

Description

Time Frame

Day 7 and 21

Title

Hypoxic load

Description

Time Frame

Day 7 and 21

Title

Hypoxic load in REM and NREM

Description

Time Frame

Day 7 and 21

Title

Arousal index

Description

Change from baseline arousal index (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.

Time Frame

Day 7 and 21

Title

Arousal index in REM and NREM

Description

Time Frame

Day 7 and 21

Title

Pulse wave amplitude (PWA) drops

Description

Change from baseline PWA drops (events/h) measured via polysomnography between the week of investigational treatment (AD128) and the week of placebo treatment.

Time Frame

Day 7 and 21

Title

Pulse wave amplitude (PWA) drops in REM and NREM

Description

Time Frame

Day 7 and 21

Title

Apnea-hypopnea index (AHI) in REM and NREM

Description

Time Frame

Day 7 and 21

Title

Percentage of REM sleep

Description

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.

Time Frame

Day 7 and 21

Title

Percentage of N1

Description

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.

Time Frame

Day 7 and 21

Title

Percentage of N2

Description

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.

Time Frame

Day 7 and 21

Title

Percentage of N3

Description

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.

Time Frame

Day 7 and 21

Title

Percentage of alpha wave

Description

Time Frame

Day 7 and 21

Title

Percentage of beta wave

Description

Time Frame

Day 7 and 21

Title

Percentage of gamma wave

Description

Time Frame

Day 7 and 21

Title

Percentage of theta wave

Description

Time Frame

Day 7 and 21

Title

Percentage of delta wave

Description

Time Frame

Day 7 and 21

Title

Reaction time PVT

Description

Time Frame

Day 7 and 21

Title

Lapse PVT

Description

Time Frame

Day 7 and 21

Title

Chronic Excessive daytime sleepiness (EDS)

Description

Time Frame

Day 7 and 21

Title

Acute Excessive daytime sleepiness (EDS)

Description

Time Frame

Day 7 and 21

Title

Sleep quality

Description

Time Frame

Day 7 and 21

Title

Fatigue

Description

Time Frame

Day 7 and 21

Title

Systolic and diastolic blood pressure

Description

Time Frame

Day 7 and 21

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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, 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raphael Heinzer, MD

Organizational Affiliation

University Hospital of Lausanne (CHUV)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Universitaire Vaudois

City

Lausanne

ZIP/Postal Code

1011

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data (IPD) could be transmitted on request after publication to researchers who provide a methodologically sound proposal.

Learn more about this trial

Effect of AD128 to Treat Obstructive Sleep Apnea

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