Effect of AD128 to Treat Obstructive Sleep Apnea

Sponsor

Raphael Heinzer (Other)

Overall Status

Completed

CT.gov ID

NCT04394143

Collaborator

Apnimed (Industry)

Enrollment

Location

Arms

8.9

Actual Duration (Months)

1.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea, Obstructive	Drug: AD128 Drug: Mannitol	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

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

Masking:

Triple (Participant, Investigator, Outcomes 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.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 20, 2020

Actual Primary Completion Date :

Jul 19, 2021

Actual Study Completion Date :

Jul 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AD128 The study specific intervention includes per oral administration of two capsules of AD128, once daily, just before lights out, for 7 days.	Drug: AD128 Oral administration of two capsules before sleep for 7 days.
Placebo Comparator: placebo Two placebo capsules (Mannitol) will be administered for the control intervention once daily, just before light outs, for one week.	Drug: Mannitol Oral administration of two capsules before sleep for 7 days. Other Names: Placebo

Arm

Intervention/Treatment

Experimental: AD128

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

Drug: AD128

Oral administration of two capsules before sleep for 7 days.

Placebo Comparator: placebo

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

Drug: Mannitol

Oral administration of two capsules before sleep for 7 days.

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

Apnea-hypopnea index (AHI) [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.

Secondary Outcome Measures

Oxygen desaturation index (ODI) [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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) [Day 7 and 21]
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) [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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 [Day 7 and 21]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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.