Studio Prospettico Per la Validazione Clinica Del Dispositivo Medico Indossabile Soundi
Phase: NA
Conditions: OSA
Sponsor: Biocubica srl

AcronymmodelStudio:
Reference  number  or  identification  code  of  
the  clinical  investigation:
Protocol  Version  Number:
SOUNDI  WEARABLE  MEDICAL  DEVICE
EUDAMEDSNR:IT-MF-000031905
PROSPECTIVE  STUDY  FOR  THE  CLINICAL  VALIDATION  OF
Study  Title:
Issuing  date:
February  15,  2023
The  information  contained  in  this  document  is  confidential  and  property  of  the  Promoter.  The  information  may  not  -  in  whole  or  in  part  -  be  
transmitted,  reproduced,  published,  or  disclosed  by  others  to  the  relevant  Ethics  Committee  and  Regulatory  Authority  without  prior  written  
authorization  from  the  Promoter,  except  to  the  extent  necessary  to  obtain  informed  consent  from  those  who  will  participate  in  the  investigation.
Confidentiality  statement
v.1.0
CLINICAL  INVESTIGATION  PLAN
STUDIO  SOUNDI
StudioSoundi
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

Biocubicasrl
IstitutoAuxologicoItalianoIRCCS-SanLuca  Hospital
20149Milan
Promoter  contact  person
Prof.CarolinaLombardi
IstitutoAuxologicoItalianoIRCCS-SanLuca  Hospital
dario.bovio@biocubica.it
Center  involved:
viaPaoloLomazzo1
Scientific  manager
Responsible  for  Supervision  on
BIOCUBICASRL
Dario  Bovio
caterina.salito@biocubica.it
UniversityMilanoBicocca,Milan
CaterinaSalito
Head  of  the  Sleep  Medicine  Service  Cardiology  Division
PiazzaleBrescia20
viaPaoloLomazzo1
PiazzaleBrescia20
Tel:3470978058
20154Milan
ePrincipal  Experimenter
Sleep  Medicine  Service  Clinics
Tel:3474835344
Tel:02/619112705
Biocubicasrl
Promoter
20254Milan
20149Milan
Device
20154Milan
ViaPaoloLomazzo1
Tel:02/36518468
GENERAL  INFORMATIONS
StudioSoundi
2/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

CodeEUDAMEDSNR:
-
OF  THE  SOUNDI  WEARABLE  MEDICAL  DEVICE
and  its  procedures.
PROSPECTIVE  STUDY  FOR  CLINICAL  VALIDATION
14155:2020,  according  to  national  and  local  regulatory  requirements  and  in  accordance  with  this  protocol
Study  Title:
declares  that  the  study  will  be  conducted  in  accordance  with  Good  Clinical  Practice  and  ISO
Prof.CarolinaLombardi
approves  this  Protocol;
v.1.0  dated  15  February  2023
_________________
Date
The  Scientific  Manager  and  Principal  Investigator:
IT-MF-000031905
___________________
Protocol  Version:
-
3/29
Confidential  –  Version  1.0  of  15  Feb  2023
APPROVAL  OF  THE  PROTOCOL
StudioSoundi
Machine Translated by Google

Acronym:
SOUNDI  wearable  medical  device
Study  design:
WEARABLE  MEDICAL  DEVICE  SOUNDI
Title  of  the  study:
No  further  follow-up  is  planned  for  subjects.
PROSPECTIVE  STUDY  FOR  THE  CLINICAL  VALIDATION  OF  THE
Promoter:
The  signals  will  be  acquired  for  approximately  8  hours  during  a  single  night  with  both  
systems  simultaneously  and  will  then  be  calculated,  via  automatic  analysis  software,  
with  subsequent  manual  correction  by  a  doctor  expert  in  sleep  medicine,  the  indices  
used,  according  to  international  guidelines,  for  the  diagnosis  of  breathing  and  sleep  
disorders.
BiocubicaSrl
Directions  for  use:
This  is  a  pre-marketing,  single-center,  prospective  clinical  investigation  to  compare  the  
effectiveness  and  safety  of  the  SOUNDI  medical  device  compared  to  polysomnography  
in  detecting  parameters  for  the  diagnosis  of  OSA  in  subjects  suspected  of  having  a  
sleep  disorder.
All  eligible  subjects  will  be  placed  with  the  Sound  device  at  the  same  time  as  a  
traditional  polysomnography  machine.
Medical  device:
CodeEUDAMEDSNR:
Among  the  recently  developed  systems  is  Soundi,  a  small,  lightweight  medical  device  
that  allows  non-invasive  monitoring  and  continuous  recording  of  vital  parameters.  The  
results  obtained  so  far  on  healthy  subjects  are  very  encouraging,  but  for  the  market  
introduction  of  SOUNDI  as  a  certified  medical  device  its  clinical  validation  on  patients  
is  necessary.
Background  Rationale:
IT-MF-000031905
Version  and  date  of  the  synopsis:  v.1.0  of  15  February  2023
Obstructive  Sleep  Apnea  Syndrome  (OSA)  is  a  highly  prevalent  sleep  disorder  and  is  
characterized  by  repeated  episodes  of  obstruction  of  the  sleep  apnea  during  sleep  
which  accompanies  intermittent  anxiety  and  sleep  fragmentation.  ment  of  this  pathology  
with  numerous  serious  repercussions  on  the  health  of  the  individual,  various  
technologically  advanced  systems  are  being  developed  which  aim  to  minimize  the  bulk  
of  the  sensors  on  the  patient,  increase  the  comfort  of  the  examination  and  reduce  the  
need  for  multiple  hospital  visits.
StudioSOUNDI
Continuous  monitoring  of  vital  parameters  for  the  diagnosis  and  follow-up  of  breathing  
and  sleep  disorders  in  adult  subjects.
4/29
Confidential  –  Version  1.0  of  15  Feb  2023
Synopsis
StudioSoundi
Machine Translated by Google

Primary  endpoint:
Endpoints:
Inclusion  criteriaed
Some  data  will  be  collected  during  a  visit
•  Evaluate  the  level  of  patient  satisfaction  in  using  the
Adult  subjects  belonging  to  the  clinical  centre,  to  carry  out  a
•  Age  between  20  and  70  years
•  Allergy  to  one  of  the  materials  in  the  device
•  Signature  of  informed  consent
•  Insufficient  cooperation/degree  of  collaboration  in  following  the  procedures  required  
by  the  study
The  following  morning  the  subject  will  return  to  the  clinics  to  return  the  two  systems  
and  complete  a  simple  satisfaction  questionnaire  prepared  for  the  study.
Secondary  objectives:
recording  of  adverse  events.
exclusion:
anthropometric  devices  will  be  positioned  simultaneously  for  polysomnography:
parameters  necessary  for  the  diagnosis  of  OSA  compared  to  polysomnography  (gold  
standard)  in  subjects  with  suspected  diagnosis  of  sleep  disorders.
•  evaluation  of  satisfaction  with  the  use  of  SOUND  I  after  the  night  of  recording  the  
parameters,  by  completing  a  questionnaire.
sleep.
Exclusion  criteria:
-  the  experimentalSoundi  device.
SOUNDI  system.
polysomnography  for  suspicion  of  a  breathing  disorder
•  Prescription,  from  clinical  practice,  to  carry  out  a  polysomnography  on  suspicion  of  a  
breathing  disorder  in
Primary  objective:
Equivalence  between  the  detection  of  parameters  useful  for  the  diagnosis  of  OSA  using  
the  SOUNDIV  system  and  standard  polysomnographic  methods.
Estimated  enrollment:
•  Participation  in  another  clinical  study.
•  Pacemaker  users.
Procedures:
•  Patients  of  both  sexes,  of  any  ethnicity
•  Evaluate  the  safety  and  tolerability  of  the  SOUNDI  system
50  subjects
•  safety  and  tolerability  of  the  SOUNDI  device  using  it
Inclusion  criteria:
•  Women  during  pregnancy
Goals:
During  the  night,  at  the  patient's  home,  the  following  parameters  will  be  acquired  for  at  
least  8  consecutive  hours:  oro-nasal  flow,  thoracic  and  abdominal  respirogram,  
snoring,  ECG,  arterial  oxygen  saturation,  body  position.
Evaluate  the  effectiveness  of  the  SOUNDI  system  in  detecting
Secondary  endpoints:
Study  population:
sleep.
-  a  traditional  polysomnigraph,  as  prescribed
StudioSoundi
5/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

The  safety  analyzes  will  be  carried  out  on  all  patients  to  whom  the  Sound  device  and  the  
polysomnography  device  have  been  applied,  regardless  of  the  validity  of  the  data  
collected.  The  safety  analyzes  will  be  of  a  descriptive  nature.
A  sample  of  50  analyzable  patients  will  guarantee  a  power  of  90%  in  determining  six  
values  of  the  parameters  detected  with  the  SOUNDI  method  which  are  in  agreement  with  
those  measured  by  polysomnography.
The  expected  duration  of  enrollment  of  all  subjects  is  approximately  6  months.
Study  duration:
For  each  parameter,  the  agreement  between  the  measurement  carried  out  with  the  
SOUNDI  method  and  the  one  carried  out  with  polysomnography  will  be  evaluated  using  
the  Bland-Altman  graph  and  the  Concordance  Correlation  Coefficient  (CCC).
Descriptive  statistics  will  be  used  to  evaluate  the  subject's  satisfaction  with  using  SOUNDI.
Statistical  considerations:
Efficacy  analyzes  will  be  carried  out  on  all  patients  who  have  completed  the  evaluation  
and  whose  data  will  be  considered  evaluable.
The  expected  duration  of  the  study  for  the  subject  is  a  maximum  of  24  hours.
The  overall  duration  of  the  study  will  be  1  year.
StudioSoundi
6/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

9
16
22
19
10.6
18
24
19
3.3
7.2
15
Systematic  errors  -  bias
Secondary  objectives
10.  Evaluation  of  the  safety  and  vigilance  of  the  medical  device
23
6.2
2.  Operational  Background  
Rational  
Background
17
Interruption  and  withdrawal  of  subjects  from  the  clinical  investigation
11.3
9.2
Effectiveness  analysis
16
20
5.1
10.3
11.  Statistics
25
8.  Duration  of  the  study
11
18
6.  Study  population  Number  of  
patients  Inclusion  
criteria  Exclusion  
criteria
Recording  of  adverse  events  Definitions  
Classification  
of  adverse  events  Predictable/expected  
adverse  events  and  effects  Reporting  of  adverse  
events  Notification  to  the  Competent  
Authorities  10.7  Consequences  on  risk  
analysis
16
23
10
Early  closure  or  suspension  of  the  study
11.4
19
4.  Study  Design  Comparison
15
16
6.3
10.4
3.  Information  on  the  medical  device  Pre-clinical  
trials  Trials  on  healthy  
volunteers  Risks  and  
benefits
17
14
19
24
Primary  endpoint
Securityanalysis
22
5.2
16
23
7.  Study  procedures  
Compliance  with  Followup  
procedures
10
11.1
3.1
8.1
4.1
9.  Evaluation  of  effectiveness
15
19
10.1
7.1
10.5
18
24
2.1
12.  Medical  device
Secondary  endpoint
Analysis  set
22
Primary  objective
1.  Abbreviations
16
8.2
11.2
14
19
3.2
10.2
23
6.1
16
10
2.2
13.  Ethical  and  regulatory  aspects
5.  Objectives  of  the  study
9.1
16
7/29
Confidential  –  Version  1.0  of  15  Feb  2023
Summary
StudioSoundi
Machine Translated by Google

27
13.2
15.1  Sourcedocuments
26
28
14.  Ownership  and  Data  Publication  Policy
13.6
17.  Steering  Committee
26
28
15.2  CaseReportForm
27
25
13.4
15.3
26
28
15.  Data  management  and  storage
13.1  Ethical  management  of  the  clinical  investigation  
Regulatory  aspects
27
13.3  Method  of  obtaining  informed  consent
18.  Bibliography
Deviations  from  the  clinical  investigation  plan  
13.7  Study  monitoring  13.8  Audited  
inspections
26
28
28
13.5  Data  processing
16.  Insurance
25
25
27
Participant  confidentiality
Document  preservation
StudioSoundi
Confidential  –  Version  1.0  of  15  Feb  2023
8/29
Machine Translated by Google

OUCH
Electroencephalogram
Arterial  oxygen  saturation
ASADE
ECG
Serious  adverse  effect  of  the  device
VolatileOrganicCompounds
Mandibular  advancement  system
USADE
ApneaHypopneaIndex
CaseReportForm
OSA
Serious  and  expected  adverse  effect  of  the  device
CPAP
GoodClinicalPractice
SAE
AE
Electrocardiogram
SeriousAdverseEvent
BMI
EEG
VOC
Serious  and  unexpected  adverse  effect  of  the  device
Obstructive  Apnea  Syndrome
HADES
CRF
ContinuousPositiveAirwayPressure
MAD
SaO2
adverseevent  (AdverseEvent)
Adverse  effect  of  the  device
BodyMassIndex
GCP
SADE
Confidential  –  Version  1.0  of  15  Feb  2023
9/29
1.  Abbreviations
StudioSoundi
Machine Translated by Google

Rational
2.1  Background
2.2
structure.
In  both  cases,  however,  the  patient  must  be  prepared  with  the  positioning  of  the  sensors  in  the  hours  preceding  
the  examination,  he  must  keep  them  worn  throughout  the  night  and  have  them  removed  in  the  morning  by  
expert  technicians  who  also  proceed  to  download  the  data  from  the  memory  on  which  they  are  collected  
during  the  night.  Some  tests  are  carried  out  at  home  and  therefore  the  patient  must  access  the  hospital  in  the  
evening  and  one  in  the  morning  for  toes  dismantle  the  equipment,  or  are  carried  out  in  the  hospital  and  in  this  
case  the  patient  remains  sleeping  inside  the
To  facilitate  easier  access  to  the  diagnosis  and  therefore  treatment  of  this  pathology  with  numerous  serious  
repercussions  on  the  health  of  the  individual,  various  technologically  advanced  systems  are  being  developed  
which  aim  to  minimize  the  bulk  of  the  sensors  on  the  patient,  increase  the  comfort  of  the  examination  and  
reduce  the  need  for  multiple  hospital  visits.  Among  the  recently  developed  systems  is  Soundi.
Soundi  is  a  small,  lightweight  medical  device  that  allows  non-invasive  monitoring  and  continuous  recording  of  
blood  pressure,  without  the  use  of  a  cuff,  and  a  whole  series  of  physiological  parameters  including  temperature,  
ECG,  ejection  fraction,  blood  pressure,  respiratory  rate,  flow,  oxygen  saturation,  apnea/hypopnea  index.  This  
innovative  device  can  completely  revolutionize  the  concept  of  monitors  sleep  aid,  currently  carried  out  using  
invasive  instrumentation  methods.  Soundi  will  allow  the  patient,  once  worn,  to  carry  out  all  his  normal  daily  
activities  without  any  discomfort.
The  parameters  that  are  acquired  during  complete  polysomnographies  are:  Electroencephalogram  (EEG),  
eye  movements,  muscle  tone  of  the  mylohyoid  muscle  and  tibial  muscles,  nasal,  thoracic  and  abdominal  
respirogram,  body  position,  oximetry,  Electrocardiogram  (ECG).
For  cardiorespiratory  polysomnography,  the  number  of  parameters  is  smaller  (nasal,  thoracic  and  abdominal  
respiration,  body  position,  oximetry,  ECG).
The  diagnosis  at  the  moment  is  carried  out  by  carrying  out  polysomnographic  tests  which  can  be  carried  out  
at  home  or  in  a  hospital  environment.  Polysomnography  is  based  on  the  nocturnal  collection  of  various  vital  
parameters  capable  of  providing  an  objective  quantification  of  the  number,  characteristics  and  intensity  of  
apneas.
Obstructive  Sleep  Apnea  Syndrome  (OSA)  is  a  highly  prevalent  sleep  disorder  and  is  characterized  by  
repeated  episodes  of  obstruction  of  the  upper  arteries  during  sleep  which  are  accompanied  by  intermittent  
anxiety  and  sleep  fragmentation.  OSA,  being  associated  with  excessive  daytime  sleepiness  and  increased  
cardiovascular  risk,  significantly  increases  mortality  and  morbidity  in  the  affected  population,  constituting  a  
public  health  problem.  These  consequences  are  significantly  reduced  by  the  early  and  appropriate  
implementation  of  specific  treatments  for  apnea  such  as  Continuous  Positive  Airway  Pressure  (CPAP),  weight  
loss,  surgery  or  mandibular  advancement  systems  (MAD).
2.  Erational  background
StudioSoundi
10/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

3.  Information  about  the  medical  device
11/29
Confidential  –  Version  1.0  of  15  Feb  2023
The  SOUNDI  medical  device  is  produced  by  the  Biocubicasrl  company.  The  measurement  unit  is  made  of  plastic  material  (PA12  
food  grade),  the  ECG  connector  cover  is  made  of  food  grade  silicone,  ECG  cables  (Spes  Medica  SpA)  are  made  of  Cu/Ag  with  
PVC  insulation  and  the  medical  double-sided  adhesive  (MED6364R)  is  made  up  of  a  double  coating,  thin,  conformable,  with  
transparent  and  moisture-resistant  polyester  film  on  both  sides.
•  Snoring
Soundi  is  a  wearable  medical  device  for  the  continuous  monitoring  of  vital  parameters  capable  of  collecting  useful  information  for  
the  diagnosis  and  follow-up  of  breathing  disorders  in  sleep.
•  Flow
•  Respiratory  rate
2.  ignition  key
The  results  obtained  so  far  on  a  population  of  healthy  subjects  are  very  encouraging  (2-3-4-5),  but  its  production  and  introduction  
on  the  market  as  a  certified  medical  device  requires  its  clinical  validation  on  patients.
•  Oxygen  saturation
Soundi  is  a  small  (diameter  of  60  m  and  height  of  12  mm),  lightweight,  which  is  applied  with  a  double-adhesive  medical  patch  on  
the  left  hemithorax  and  can  record  the  parameters  over  24  hours  for  up  to  15  consecutive  days.  Equipped  with  a  rechargeable  
battery,  it  is  capable  of  providing  continuous  measurement  of  the  main  physiological  parameters.
1.  multi-sensor  measuring  unit  (Figure  2)
Simultaneous  collection  of  a  number  of  parameters  using  a  single  vital  sign  detection  device  can  provide  close,  long-term,  low-
cost  and  shareable  health  status  monitoring,  with  the  potential  to  improve  health  management  and  quality  of  life,  promote  both  
early  intervention  and  proactive  care  and  reduce  healthcare  costs.
•  Temperature
•  ECG
Soundi  is  also  able  to  record  environmental  parameters  in  which  the  individual  lives,  in  particular  it  detects  temperature,  relative  
humidity,  pressure,  CO2  equivalent,  Volatile  Organic  Compounds  (VOC)  produced  by  human  breathing  (for  example  CO)  and  
by  the  environment  (for  example  formaldehyde).
•  Heart  rate
Specifically,  the  parameters  Sound  detects  are:
•  Numeropassi.
Soundi  is  made  up  of  the  following  components  (Figure  1):
The  current  prototype  of  the  Soundi  device  was  developed  on  the  basis  of  a  technology  patented  by  
Biocubica  (Italian  patent  no.  102016000052588  “Physiological  monitoring  device”  and  European  patent  
EP3.248.541  “Physiological  monitoring  device”)(1)  and  is  equipped  with  the  ability  to  listen,  through  a  
particular  bell  shape,  to  all  the  sound  evidence  nothing  from  our  body  and  generated  at  different  
frequencies  by  different  organs  and/or  muscles  and  tissues,  and  transduce  them,  through  a  series  of  
sensors  and  with  appropriate  algorithms,  into  different  vital  signals.
•  Nocturnal  posture
StudioSoundi
Machine Translated by Google

Figure  1.  SOUNDI:1.Measurement  unit;2.Ignition  key;3.Double-sided  medical  tape.
Soundi  is  supplied  with  the  following  accessories:  •  1-
channel  ECG  cable  •  USB  
cable  to  allow  charging  of  the  rechargeable  battery  and  connection  to  the  PC  •  power  supply
Figure2.  Image  of  the  SOUNDI  multisensor  measurement  unit
3.  a  double-adhesive  medical  plaster.
•  softwarepcSOUNDIDOC.
The  device  will  be  used  for  full  cardiorespiratory  monitoring.
Being  a  wearable  device  also  intended  for  non-hospitalized  patients,  SOUNDI  is  also  intended  to  be  used  in  a  home  environment.
StudioSoundi
12/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

The  recording  file  downloaded  onto  the  experimenter's  PC  will  then  be  analyzed  with  the  Remlogic  software  already  in  
use  at  the  center  for  the  analysis  of  polysomnographic  signals.
Figure  3  shows  the  SOUNDI  system  diagram.
Figure3.  SOUNDI  system
Figure  4  shows  the  block  diagram  of  the  hardware  part  of  the  device.
SOUNDIDOC  is  the  software  for  managing  the  SOUNDI  device.  It  is  a  desktop  software  mainly  composed  of  two  
sections/functionalities:
2.  DownloadExam.
1.  Examination  programme
The  SOUNDI  device  records  in  internal  memory  the  physiological  data  of  the  monitored  person.  The  data  is  then  
downloaded,  via  USB  cable,  to  the  PC  to  be  converted  into  a  file  with  standard  edf,  the  same  format  as  the  file  returned  
by  the  standard  polysomnography  device.
StudioSoundi
13/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

3.1  Pre-clinical  tests
3.2  Tests  on  healthy  volunteers
14/29
Confidential  –  Version  1.0  of  15  Feb  2023
extracted  the  main  parameters  linked  to  respiratory  disorders  in  sleep  with  an  accuracy  of  approximately  97%.
The  SOUNDI  device  does  not  require  any  particular  maintenance  if  the  following  conditions  are  met:
_SOUNDI_06_FT_01_Proveditipo).
Rossietal  (5)  used  Soundi  on  a  group  of  20  healthy  subjects  to  carry  out  acquisitions  of  physiological  signals  during  sleep.  Through  
an  algorithm  based  on  artificial  intelligence  they
The  Experimenter  will  be  required  to  carefully  read  the  manual  before  using  the  device  so  as  to  be  aware  of  important  information  
such  as  safety  warnings,  dangers,  precautions,  calibration,  use,  contraindications,  maintenance  and  storage  etc...
-  electrical  safety  carried  out  at  the  MTICINTERCERT  certified  laboratory  (annex  9
Based  on  measurements  taken  in  five  male  volunteers  who  had  no  previous  signs  of  cardiovascular  disease,  Rossietal  (4)  suggested  
a  robust  deep  learning  model  to  improve  the  estimation  of  the  variables  extractable  from  the  signals  acquired  by  the  Soundi.
User  manual.
verifying  compliance  of  the  SOUNDI  medical  device  with  the  European  Medical  Device  Directive  using  biocompatibility  and  
electromagnetic  compatibility  testing
Furthermore,  Marzoratietal  (3)  have  proposed  an  innovative  algorithm  to  improve  the  accuracy  in  the  detection  of  signals  recorded  
by  Soundi  during  24  hours.
The  SOUNDI  medical  device  will  be  provided  to  the  Investigator  together  with  the  current  version  of  the
The  preclinical  evaluation  of  the  SOUNDI  device  concerned:
Marzoratietal  (2)  demonstrated  in  a  court  of  20  healthy  subjects  that  the  use  of  Sound  for  non-invasive  measurement  of  blood  
pressure  produces  results  with  accuracy  comparable  to  that  of  a  normal  blood  pressure  monitor.
Figure4.  Block  diagram
The  SOUNDIDOC  software  package  will  be  installed  by  sponsor  personnel  on  a  PC  indicated  by  the  experimenter.  A  sufficient  
number  of  SOUNDI  device  samples  to  conduct  the  investigation
-
The  results  obtained  so  far  on  a  population  of  healthy  subjects  are  very  encouraging  (2-3-4-5).
clinic  will  be  provided  at  the  center.
o  Storage:  The  SOUNDI  device  must  be  stored  in  a  dust-free  environment,  at  a  temperature  between  -25°C  and  +70°C  
and  at  a  relative  humidity  of  less  than  93%.
-
o  Cleaning  the  device:  The  SOUND  In  device  should  never  be  immersed  in  any  liquid.  The  unit  should  be  cleaned  with  
a  neutral  soap  solution  with  a  soft  cloth.  Never  use  a  sharp  tool  to  remove  dirt,  as  it  will  scratch  the  surface.
the  verification  and  validation  of  the  software  reported  in  the  Technical  File,  in  the  file  11_FT_01_VerificaRequisitiSW.
StudioSoundi
Machine Translated by Google

-  Allergic  reaction  to  double-sided  adhesive  components
San  Luca  Hospital  in  Milan.
medical
All  patients  belong  to  the  Sleep  Medicine  Center  of  the  Italian  Auxological  Institute  IRCCS-
The  study  expects  to  enroll  50  patients.
-  Discomfort  associated  with  positioning/removing  the  measurement  unit  using  double-sided  adhesive
The  main  risks  associated  with  the  use  of  the  SOUNDI  device  by  the  subjects  included  in  the  clinical  investigation  are:
This  is  a  pre-marketing,  single-center,  prospective  clinical  investigation  to  compare  the  effectiveness  and  safety  of  the  SOUNDI  
medical  device  compared  to  polysomnography  in  detecting  parameters  for  the  diagnosis  of  OSA  in  subjects  suspected  of  having  a  
sleep  disorder.
As  a  comparison  to  evaluate  the  effectiveness  of  the  SOUND  In  device  in  detecting  the  parameters  for  the  diagnosis  of  OS,  an  
Embletta  polysomnography  machine  (Natus)  will  be  used.  This  device  is  already  in  use  at  the  clinical  center  and  will  be  used  
according  to  clinical  practice  for  polysomnography.
The  simultaneous  collection  of  vital  signs  may  allow  for  an  early  diagnosis  of  OSA  in  subjects  suspected  of  having  a  sleep  disorder.
No  further  follow-up  is  planned  for  subjects.
Furthermore,  the  clinical  validation  of  the  SOUND  I  device  on  patients  will  allow  the  marketing  of  a  small,  handy  and  inexpensive  
device  for  the  continuous  monitoring  of  vital  parameters,  capable  of  collecting  useful  information  for  the  early  diagnosis  or  follow-up  
of  breathing  disorders  in  sleep.
The  intrinsic  risks  most  related  to  the  design  of  the  device  (explosion/fire  of  the  battery,  electrocution  linked  to  electrical  leakage,  
emission  of  electromagnetic  radiation,  etc.)  were  evaluated  and  minimized  in  the  design  phase  and  verified  through  laboratory  tests  
(electrical  safety  and  electromagnetic  compatibility).
The  signals  will  be  acquired  for  approximately  8  hours  during  a  single  night  with  both  systems  simultaneously  and  will  then  be  
calculated,  via  automatic  analysis  software,  with  subsequent  manual  correction  by  a  doctor  expert  in  sleep  medicine,  the  indices  
used,  according  to  international  guidelines,  for  the  diagnosis  of  breathing  and  sleep  disorders.
These  risks  will  be  minimized  by  the  training  of  the  personnel  who  will  place  and  remove  the  device  from  the  subject  and  by  the  
exclusion  from  the  study  of  subjects  with  a  known  allergy  to  the  components  of  the  double-sided  adhesive.
After  signing  the  informed  consent,  the  Sound  device  will  be  placed  in  all  eligible  subjects  and  at  the  same  time  as  a  traditional  
polysomnography  device  the  activation  of  the  devices  for  the  acquisition  of  the  parameters  will  be  programmed  so  that  it  begins  
when  the  subject  lies  down.
4.  Study  design
4.1  Comparison
3.3  Risks  and  benefits
StudioSoundi
Confidential  –  Version  1.0  of  15  Feb  2023
15/29
Machine Translated by Google

6.1  Number  of  patients
6.2  Inclusion  criteria
5.2  Secondary  objectives
5.1  Primary  objective
6.3  Exclusion  criteria
•  Pacemaker  users.
•  Signature  of  informed  consent
•  Allergy  to  one  of  the  materials  in  the  device
compared  to  polysomnography  (gold  standard)  in  subjects  with  a  suspected  diagnosis  of  sleep  disorders.
•  Participation  in  another  clinical  study.
Patients  will  be  identified  by  a  unique  alphanumeric  code  which  will  be  assigned  at  the  time  of  enrollment  based  on  the  center  
code  and  enrollment  sequence  (e.g.  Aux-001).
Evaluate  the  effectiveness  of  the  SOUNDI  system  in  detecting  parameters  necessary  for  the  diagnosis  of  OSA
study
To  document  the  patient  selection  bias,  all  reasons  for  non-participation  in  the  study  will  be  recorded  on  a  specific  form  (Screening  
Log).
•  Insufficient  cooperation/degree  of  collaboration  in  following  the  procedures  required  by  the
The  study  involves  the  enrollment  of  50  patients  belonging  to  a  single  Italian  centre:  Sleep  Medicine  Center  of  the  Italian  
Auxological  Institute  IRCCS  -  San  Luca  Hospital  in  Milan.
•  Prescription,  from  clinical  practice,  to  carry  out  a  polysomnography  on  suspicion  of  a  sleep  breathing  disorder.
•  Women  during  pregnancy
All  subjects  enrolled  in  the  study  will  undergo  polysomnography  (monitoring
•  Evaluate  the  level  of  patient  satisfaction  in  using  the  SOUNDI  system
•  Age  between  20  and  70  years
•  Patients  of  both  sexes,  of  any  ethnicity
•  Evaluate  the  safety  and  tolerability  of  the  SOUNDI  system
7.  Study  procedures
5.  Objectives  of  the  study
6.  Study  population
StudioSoundi
Confidential  –  Version  1.0  of  15  Feb  2023
16/29
Machine Translated by Google

Follow  up
7.1  Compliance  with  procedures
7.2
17/29
Confidential  –  Version  1.0  of  15  Feb  2023
subject  will  be  reported  in  the  electronic  data  collection  form  (CRF).
The  patient  will  be  instructed  by  the  Investigator  on  the  correct  management  of  the  devices.
•  AHIcentral
The  anthropometric  data  (age,  BMI,  neck  and  abdomen  circumference),  the  parameters  deriving  from  the  analysis  of  
the  acquisitions  of  the  instrumental  polysomnographic  signal  and  the  responses  to  the  questionnaire  provided  by  the
theSoundiexperimentaldevice.
•  ApneaHypopneaIndex(AHI)totalandsupine
•  Percentages  of  time  spent  in  different  body  positions.
-  a  traditional  polysomnigraph,  as  prescribed
RemLogic,  via  automatic  analysis  software,  with  subsequent  manual  correction  by  a  doctor  expert  in  sleep  
medicine,  the  following  indices  used,  according  to  international  guidelines,  for  the  diagnosis  of  respiratory  
and  sleep  disorders:
•  Minimum  heart  rate
On  the  afternoon  before  the  night  of  the  evaluation,  at  the  Sleep  Medicine  Service  clinic,  each  object  will  
be  placed
The  signals  acquired  with  both  systems  simultaneously  will  be  processed  by  the  software
•  Minimum  SaO2
•  Average  heart  rate
Unless  particular  problems  are  reported  to  the  patient  (adverse  events  or  effects  related  to  the  use  of  the  
device  in  the  study)  which  will  be  followed  by  specific  assessments,  a  follow-up  will  not  be  necessary.
nocturnal  cardiorespiratory  for  the  diagnosis  of  apnea  in  sleep)  with  traditional  polysomnography  (Embletta,  Natus)  according  to  
normal  clinical  practice  and  at  the  same  time  as  data  acquisition  with  the  Soundi  system.
During  the  night,  at  the  patient's  home,  the  following  parameters  will  be  acquired  with  two  systems:  oro-nasal  
flow,  thoracic  and  abdominal  respirations,  snoring,  ECG,  arterial  oxygen  saturation  (SaO2),  body  position.
-
•  Average  arterial  oxygen  saturation  (SaO2).
The  following  morning  the  subject  will  return  to  the  clinics  to  return  the  two  systems  which  will  be  detached  
by  the  medical  staff.  There,  the  subject  will  be  asked  to  fill  out  a  simple  satisfaction  questionnaire  prepared  
for  the  study.
Furthermore,  the  Experimenter  will  program  the  devices  to  begin  recording  the  parameters  at  the  moment  
the  subject  expects  to  recharge  and  continue  for  at  least  8  consecutive  hours.
•  OxygenDesaturationIndex(ODI)
•  TimewithSaO2<90%
All  tests  without  artifacts  invalidating  the  interpretation  of  one  or  more  signals  acquired  for  at  least  4  hours  of  
sleep  will  be  considered  valid.
During  the  visit,  the  following  anthropometric  data  will  be  collected:  age,  BodyMassIndex  (BMI),  neck  circumference  and  
abdomen.
•  AHIobstructive
StudioSoundi
Machine Translated by Google

The  overall  duration  of  the  study  will  be  1  year.
-  an  adverse  event  (related  or  unrelated  to  the  study  device)  which,  in  the  opinion  of  the  Principal  Investigator,  does  not  
allow  the  continuation  of  the  study  itself.
The  Promoter  reserves  the  right  to  interrupt  or  suspend  the  study  at  any  time  for  reasonable  medical,  safety,  or  administrative  
reasons.
The  start  of  the  study  is  defined  by  the  date  of  signing  the  consent  of  the  first  patient  and  the  end  of  the  study  by  the  last  data  
analysis  of  the  last  patient.
-  lack  of  adherence  to  the  procedures  required  by  the  study  protocol  on  the  part  of  the  patient
•
The  expected  duration  of  the  study  for  the  subject  is  a  maximum  of  24  hours.
the  change  in  the  patient's  clinical-functional  conditions  that  do  not  allow  participation
•  Suspension  or  termination  of  Ethics  Committee  approval
In  the  event  of  suspension,  the  study  may  be  resumed  once  issues  of  safety,  protocol  compliance  or  data  quality  have  been  resolved  to  
the  satisfaction  of  the  Sponsor  and  the  Ethics  Committee.
The  expected  duration  of  enrollment  of  all  subjects  is  approximately  6  months.
withdrawal  of  consent  by  the  patient
The  reasons  for  stopping  the  study  will  be  recorded  in  CRF.
Patients  excluded  from  the  study  and  who  cannot  obtain  the  data  required  by  the  study  protocol  will  be  replaced  to  reach  the  
required  number.
•  Any  serious  or  persistent  case  of  non-compliance  with  the  legislation
Reasons  for  discontinuing  a  patient's  participation  in  the  study  may  include:
Each  patient  is  free  to  withdraw  from  the  study  at  any  time  or  his  participation  may  be  interrupted  by  decision  of  the  trial  for  
safety,  behavioral  or  reasons
If  the  study  is  interrupted  for  any  of  the  reasons  listed  above,  the  measurements  taken  will  not  be  considered  in  the  statistical  
analysis.
Unless  particular  problems  are  reported  to  the  patient  (adverse  events  or  effects  related  to  the  use  of  the  device  in  the  study)  
which  will  be  followed  by  specific  assessments,  a  follow-up  will  not  be  necessary.
administrative.
•  Determination  of  an  unexpected,  significant  or  unacceptable  risk  to  participants
-
Circumstances  that  may  justify  interruption  or  suspension  of  the  study:
The  feedback  from  the  data  is  excessively  different  from  that  expected.
-
The  Sponsor  will  notify  the  Ethics  Committee  and  the  Principal  Investigator  of  the  decision  to  suspend  or  interrupt  the  study  with  
the  reasons.  It  will  also  provide  the  trial  with  specific  instructions  to  inform  the  patients  and  indications  on  the  procedures  to  be  
followed.
Early  closing  or  suspension  of  the  study
8.2
Interruption  and  withdrawal  of  subjects  from  the  clinical  investigation
8.1
8.  Duration  of  the  study
StudioSoundi
18/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

9.1
10.1  Recording  of  adverse  events
9.2  Secondary  endpoint
Primary  endpoint
10.2  Definitions
Adverse  events  (AEs)  will  be  collected  by  signing  informed  consent  at  the  end  of  the  study  procedures  or  
until  they  are  resolved  or  stabilized  or  until  follow-up  is  no  longer  possible.
Adverse  Event  (AE)
The  investigator  is  responsible  for  detecting  and  documenting  in  the  patient's  medical  records  all  twenty  that  
occur  during  the  study,  regardless  of  their  severity  and  relationship  to  the  device  and  their  recording  in  the  
dedicated  section  of  the  CRF.
Note2:  For  users  or  other  persons  this  is  limited  to  events  relating  to  the  SOUNDI  medical  device.
The  secondary  endpoint  of  effectiveness  of  the  clinical  investigation  is  the  evaluation  of  satisfaction  with  the  
use  of  SOUND  I  after  the  night  of  recording  the  parameters,  through  the  patient's  completion  of  a  
questionnaire  prepared  for  the  study.
AE  means  any  harmful  clinical  event,  disease,  unintentional  injury  or  favorable  clinical  sign  (including  an  
abnormal  laboratory  result)  that  occurs  in  subjects,  users  or  other  persons  as  part  of  a  clinical  investigation,  
whether  or  not  the  event  is  related  to  the  device  under  investigation
The  clinical  investigation  also  aims  to  evaluate  the  safety  and  tolerability  of  the  SOUNDI  device  by  recording  
adverse  events  (secondary  safety  endpoint).
The  primary  endpoint  of  the  study  is  the  equivalence  between  the  detection  of  parameters  useful  for  the  diagnosis  
of  OSA  using  the  SOUNDIV  system  and  standard  polysomnographic  methods.
Serious  Adverse  Event  (SAE)
Serious  Adverse  Event  (SAE)  means  any  adverse  event  that  has  one  of  the  following  consequences:
•  undeath;
Note  1:  This  definition  includes  events  related  to  the  wearable  wireless  device  (SOUNDI),  polysomnography  
and  any  other  procedures  covered  by  the  study  protocol.
•  a  serious  worsening  of  the  subject's  health  conditions  which  resulted  in:
9.  Evaluation  of  effectiveness
10.  Evaluation  of  the  safety  and  vigilance  of  the  medical  device
StudioSoundi
Confidential  –  Version  1.0  of  15  Feb  2023
19/29
Machine Translated by Google

10.3  Classification  of  adverse  events
Confidential  –  Version  1.0  of  15  Feb  2023
20/29
Note  1:  A  planned  hospitalization  for  a  pre-existing  condition,  or  a  procedure  required  by  the  clinical  investigation  plan,  without  
serious  deterioration  in  health,  is  not  considered  an  SAE.
Device  defect
congenital
Serious  and  unexpected  adverse  effect  (USADE,  unanticipated  serious  adverse  device  effect)  means  an  adverse  effect  of  the  
device  not  identified  in  the  updated  version  of  the  risk  analysis.
•  fetal  distress,  fetal  death  or  a  malformation  or  physical  or  intellectual  disability
Adverse  Device  Effect  Serious  and  Expected  (USADE)
ii)  a  permanent  damage  to  a  body  structure  or  function;  iii)  the  need  for  hospital  admission  of  the  
patient  or  its  prolongation;
Anticipated  serious  adverse  device  effect  (ASADE)  means  an  adverse  effect  of  the  device  already  identified  in  the  risk  analysis.
10.3.1  Evaluation  of  the  severity  of  the  event
(i)a  life-threatening  illness  or  injury;
Serious  Adverse  Device  Effect  (SADE)
Serious  and  Expected  Adverse  Device  Effect  (ASADE)
The  investigator  and/or  the  Promoter  will  provide  an  assessment  of  the  seriousness,  severity  of  the  event  
and  the  causal  relationship  with  the  device  under  study  and  will  also  record  the  duration,  outcome  and  
actions  taken.
Serious  adverse  device  effect  (SADE)  means  a  serious  adverse  effect  related  to  the  use  of  the  SOUNDI  device.
Adverse  device  effect  (ADE)  means  an  adverse  event  related  to  the  use  of  the  SOUNDI  wearable  wireless  device.
The  intensity  of  the  AE  will  be  characterized  as  follows:
Adverse  Device  Effect  (ADE)
Device  defect  means  any  deficiency  in  the  identity,  quality,  durability,  reliability,  safety  or  performance  of  a  device  under  
investigation,  including  malfunction,  errors  in  use  or  inadequacy  of  information  provided  by  the  manufacturer.
StudioSoundi
Machine Translated by Google

clinical  judgement,  including  all  relevant  factors  such  as  time  course  and  latency,  known  properties  of  the  device  
and  alternative  explanations  (e.g.  medical  history,  concomitant  diseases)  and  must
•  unclassifiable:  clinical  event  for  which  the  information  received  is  inadequate  and/or
•  resolved  with  consequences:  the  patient  recovered  from  the  event,  but  with  clinical  consequences.
•  unlikely:  the  relationship  to  the  use  of  the  device  does  not  appear  relevant  and/or  the  event  can  be  reasonably  
explained  by  another  cause,  but  additional  information  may  be  obtained.
10.3.2  Evaluation  of  the  relationship  to  the  medical  device
resolved:  the  patient  has  returned  to  the  condition  prior  to  the  event
The  clinical  outcome  of  the  AE  or  SAE  will  be  recorded  as  follows:
O  severe:  marked  limitation  of  activity,  usually  requires  some  assistance;  intervention
•  probable:  the  relationship  with  the  use  of  the  experimental  device  seems  relevant  and/or  the  event  cannot  be  
reasonably  explained  by  another  cause,  but  additional  information  can  be  obtained.
•
For  both  AE  and  SAE,  the  experimenter  will  record  the  start  date  and  time  and  the  end  date  and  time  of  the  event.
O  moderate:  from  mild  to  moderate  limitation  of  activity;  some  assistance  may  be  necessary;
•  causal  relationship:  event  is  associated  with  the  medical  device  or  a  procedure  beyond
ongoing:  the  patient  has  not  recovered  and  the  symptoms  continue
The  relationship  between  the  use  of  the  medical  device  and  the  occurrence  of  each  adverse  event  must  be  evaluated  
and  classified.  During  the  evaluation  of  causality,  the  investigator  must  use
O  mild:  transient  discomfort  or  mild;  no  activity  limitations;  no  intervention
Please  consult  relevant  documents,  such  as  instructions  for  use,  clinical  protocol  or  risk  analysis  report,  as  all  
foreseeable  serious  adverse  events  and  potential  risks  are  listed  and  assessed  in  these  documents.
•  not  related:  the  relationship  with  the  medical  device  or  procedure  can  be  excluded.
contradictory  and  do  not  allow  reasonable  ascertainment.
•  death
doctor/therapy  required,  hospitalization  possible.
•  possible:  the  relationship  with  the  use  of  the  device  is  weak,  but  cannot  be  completely  ruled  out.  Alternative  
causes  are  possible  (e.g.  a  concomitant  disease,  a  treatment,  another  device,  etc.).  Cases  in  which  the  
relationship  cannot  be  established  or  sufficient  information  is  not  available  should  be  classified  as  possible.
any  reasonable  doubt
none  or  minimal  medical  intervention/therapy  required.
10.3.4  Outcome  of  the  event
The  Investigator  and  the  Sponsor  will  separately  evaluate  and  document  the  relationship  between  an  adverse  event  
and  the  experimental  device  or  procedure,  according  to  the  following  classification  criteria:
doctor/therapyrequired.
10.3.3  Duration  of  the  event
•
StudioSoundi
21/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

Reporting  of  adverse  events
10.5
Predictable/expected  adverse  events  and  effects
10.6  Notification  to  the  Competent  Authorities
22/29
Confidential  –  Version  1.0  of  15  Feb  2023
or  none:  no  treatment  or  action  taken.
The  Investigator  must  immediately  communicate  to  the  Sponsor  of  the  clinical  study  and  in  any  case  no  more  
than  3  days  after  the  event:
In  the  case  of  USADE,  the  Sponsor  or  its  delegate  will  report  the  results  of  the  evaluation  to  the  Competent  
Authority  and  the  Principal  Participating  Investigator  in  accordance  with  the  applicable  regulations.
or  non-pharmacological  treatment:  e.g.  physiotherapy
All  adverse  events  (serious  and  non-serious)  and  medical  device  defects  will  be  collected,  carefully  evaluated  
and  documented  in  the  medical  record  and  in  the  CRF  by  the  Principal  Investigator.
Events  will  be  reviewed  by  the  Promoter  to  determine  any  reporting  obligations.  Reporting  will  take  place  
within  the  time  limits  described  in  the  applicable  regulations.
as  follows:  o  
pharmacological  treatment:  e.g.  inflammatory  drugs
The  reporting  of  adverse  events  will  comply  with  what  is  reported  in  the  national  reference  legislation  
(DLvo37/2010),  in  the  UNIENISO14155  technical  standard  and  in  the  MEDDEV2.7/3  guidelines.
The  treatment  or  action  taken  following  the  onset  of  an  AE  or  SA  will  be  recorded
If/when  additional  information  is  available,  the  Investigator  will  send  a  follow-up  SAE  in  the  same  manner  and  
timing  as  the  initial  SAE.
dario.bovio@biocubica.it.
10.3.5  Actions  Undertaking
Predictable  potential  adverse  effects  are  exclusively  linked  to  the  use  of  double-sided  medical  adhesive  
and  may  include  skin  irritation,  inflammation  or  other  negative  reactions.
The  communication  will  be  made  using  the  appropriate  form  to  be  sent  to:
Furthermore,  the  Investigator  will  have  to  do  what  is  necessary  for  the  safety  and  well-being  of  the  subject,  
until  recovery  or  clinical  stabilization.
More  information  on  expected  adverse  effects  and  their  management  is  available  in  the  investigator's  
dossier.
10.4
c)  any  new  conclusions  relating  to  each  event  referred  to  in  letters  from  a)  to  c).
a)  any  SAAnd  b)  
any  defect  in  a  device  which  could  have  caused  a  serious  adverse  event  in  the  absence  of  appropriate  
measures  or  intervention  or  if  the  circumstances  had  been  less  favourable;
The  following  events  must  be  reported  by  the  Promoter  to  the  Competent  Authorities  (Ministry  of
StudioSoundi
Machine Translated by Google

11.2  Securityanalysis
10.7  Consequences  on  risk  analysis
11.1  Effectiveness  analysis
11.Statistics
The  Promoter  must  forward  the  events  specified  above  to  the  Ministry  of  Health  and  the  Ethics  Committee  with  the  following  
deadlines:
•  immediately  and  no  later  than  2  days  in  the  case  of  SAE  with  imminent  danger  to  life,
death;
•  immediately  and  no  later  than  7  days  in  other  cases  SAE.
•  any  defect  in  a  device  that  could  have  caused  a  serious  adverse  event  in  the  absence  of  appropriate  measures  or  
intervention  or  if  the  circumstances  had  been  less  favourable;
•  any  new  conclusion  relating  to  each  event  referred  to  in  the  previous  2  points.
•  any  serious  adverse  event  (SAE)  for  which  there  is  a  causal  relationship,  even  if  only  reasonably  possible,  with  the  device  
under  investigation,  the  comparison  product  or  the  investigation  procedure;
Health):
If  serious  adverse  effects  occur,  defects  in  the  device  which  could  have  produced  a  serious  adverse  effect,  the  Promoter  will  
evaluate,  together  with  the  Principal  Investigator,  whether  to  update  the  risk  analysis  and  implement  preventive  or  corrective  
actions.
The  continuous  variables  will  be  reported  as  the  mean  value  and  standard  deviation  or  as  the  median  and  interquartile  range  in  
the  case  of  non-normally  distributed  data.  Therefore,  for  each  parameter  the  agreement  between  the  measurement  carried  out  
with  the  SOUNDI  method  and  the  one  carried  out  with  polysomnography  (gold  standard)  will  be  evaluated  using  the  Bland-Altman  
graph  and  the  Concordance  Correlation  Coefficient  (CCC)  [6].  In  short,  this  graph  represents  the  value  of  the  differences  of  the  
measurements  carried  out  with  two  methods  differ  from  their  average[7].  The  CCC  varies  between  -1  and  1,  values  between  0.61  
and  0.80  indicate  substantial  agreement  while  values  greater  than  0.81  almost  perfect  agreement  according  to  the  Landisand  Koch  
scale  [8].
Descriptive  statistics  will  be  used  to  evaluate  the  subject's  satisfaction  with  using  SOUNDI.
The  safety  analyzes  will  be  carried  out  on  all  patients  to  whom  the  Sound  device  and  the  polysomnography  device  have  been  
applied,  regardless  of  the  validity  of  the  data  collected.
In  general,  safety  analyzes  will  be  descriptive  in  nature.  The  frequency,  severity,  severity  and  causal  relationship  of  adverse  events  
will  be  tabulated.
Both  the  number  and  percentage  of  events  and  patients  experiencing  an  event  will  be  presented.  Additionally,  adverse  events  that  
led  to  study  suspension  and  device  defects  reported.
StudioSoundi
23/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

11.4  Systematic  errors  -  bias
11.3  Analysis  set
12.Medical  device
The  following  will  be  excluded  from  the  statistical  evaluation:
To  document  the  patient  selection  bias,  all  reasons  for  non-participation  in  the  study  will  be  recorded  on  a  specific  form  
(Screening  Log)  and  considered  in  the  subsequent  statistical  analysis.
Efficacy  analyzes  will  be  carried  out  on  all  patients  who  have  completed  the  evaluation  and  whose  data  will  be  considered  evaluable.
This  will  then  be  followed  by  manual  correction  by  the  operator  expert  in  sleep  medicine  who  is  blind  to:  the  identity  of  the  subject  
under  examination,  the  device  with  which  the  data  are  obtained  and  the  outcome  of  the  same  parameters  obtained  with  the  
comparison  device.
Any  distortions  will  be  prevented  by  deriving  the  indices  used  for  the  diagnosis  of  respiratory  and  sleep  disorders  from  both  
methods  (Polysomnigraph  and  Soundi)  using  the  same  automatic  analysis  software  (RemLogic).
A  sample  of  50  analyzable  patients  will  guarantee  a  power  of  90%  in  determining  six  values  of  the  parameters  detected  with  the  
SOUND  I  method  are  in  agreement  with  those  measured  by  polysomnography.  The  estimate  was  made  considering:  i)  a  z-head  
and  a  tail  with  a  significance  level  of  5%;  ii)  a  value  of  the  CCCparia  0.60  below  H0;  iii)  a  value  of  the  CCCparia  0.81  below  
H1 .Sample  sizing  was  performed  using  PASS2021(PowerAnalysisandSampleSizeSoftware(2021).NCSS,LLC.Kaysville,Utah,USA).
It  is  planned  to  use  2  experimental  devices  (SOUNDI  system,  Biocubica)  and  1  product
How  to  minimize  these  biases  is  further  detailed  in  the  dossier  for  the  investigator.
Sample  size.
data  obtained  from  measurements  of  patients  excluded  from  the  study.
-
In  the  event  of  bad  positioning,  the  measurement  results  may  be  compromised  and  the  signal  may  be  incomparable  with  that  
acquired  by  the  polysomnography  machine.  In  this  last  case  the  measurement  is  unusable  for  the  study  and  the  patient  data  will  
not  be  included  in  the  effectiveness  analysis.
The  safety  analyzes  will  be  carried  out  on  all  patients  to  whom  the  Soundi  device  and  the  polysomnography  device  (safety  
population)  have  been  applied,  regardless  of  the  validity  of  the  data  collected.
malposition  of  the  device
Specifically,  a  check  of  all  the  sensors  when  the  device  is  started  was  included  in  the  design  phase.  In  the  event  of  a  malfunction  
of  one  of  them,  it  is  signaled  by  a  flashing  red  LED.  In  this  case  the  measurement  can  be  repeated  with  another  device  supplied.
-  all  measurements  lasting  less  than  4  ha  cause  the  malfunction/
Impairment  of  the  results  or  interpretation  of  the  results  may  be  caused  by  malposition  or  malfunction  of  the  device.
StudioSoundi
24/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

13.  Ethical  and  regulatory  aspects
13.2  Regulatory  aspects
13.1  Ethical  management  of  the  clinical  investigation
13.3  Method  of  obtaining  informed  consent
If  a  device  is  lost  or  damaged,  the  Investigator  will  notify  it
The  clinical  investigation  is  subject  to  review  and  approval  by  the  Competent  Authority  and  the  Ethics  Committee.
The  devices  will  be  stored  centrally  in  a  secure  location  where  only  authorized  personnel  can  access  them  and  at  a  temperature  
between  -25°C  and  +70°C  and  a  relative  humidity  of  less  than  93%,  as  indicated  by  the  manufacturer,  until  delivery  to  the  patient.
The  Investigator  will  be  responsible  for  keeping  track  of  the  experimental  devices  from  their  delivery  to  the  center  until  they  are  
returned  to  the  Sponsor  at  the  end  of  the  study.
The  Principal  Investigator  is  responsible  for  the  correct  conduct  of  the  clinical  investigation  in  accordance  with  the  provisions  of  
this  protocol,  any  future  amendments,  the  other  procedures  envisaged  by  the  Sponsor  and  the  Good  Clinic  Practice  (GCP).
The  experimental  SOUNDI  devices  will  be  supplied  by  the  Promoter  and  will  be  identified  by  a  batch  number  and  a  serial  number.
and  in  accordance  with  the  Medical  Devices  Regulation  (EU)  2017/745  and  ISO14155:2020.
Before  recruitment,  each  subject  will  be  informed  of  the  nature  and  purpose  of  the  clinical  investigation,  procedures,  duration  and  
risks  and  benefits.
Furthermore,  withdrawal  from  study  is  possible  at  any  time  without  the  need  for  any  explanation.
The  clinical  investigation  will  be  conducted  in  full  compliance  with  the  provisions  of  international  legislation  and  its  national  
transposition  regarding  clinical  trials  and  the  principles  of  the  Helsinki  Declaration  with  the  aim  of  ensuring  maximum  protection  
of  the  subjects  involved.
comparison  (polysomnograph,  Embletta,  Natus).
The  Investigator  will  inform  the  subject  that  participation  in  the  study  is  completely  voluntary  and  that  in  no  way  would  refusal  
jeopardize  future  treatment  or  relationships  with  his  doctor.
The  polysomnograph  (Embletta,  Natus)  is  already  present  at  the  center  as  it  is  used  for  clinical  practice.
If  during  the  course  of  the  trial,  substantial  changes  to  the  study  protocol  become  necessary,  the  Sponsor  will  submit  an  
appropriate  request  for  an  amendment  to  the  Ethics  Committee  and  the  Competent  Authority.  The  authorization  of  the  Ethics  
Committee  and/or  the  Competent  Authority  will  be  necessary  before  their  application.
immediately  to  the  Promoter.
The  written  approval  of  the  relevant  Ethics  Committee  must  be  obtained  before  the  start  of  any  study-related  procedure  and  
must  be  documented  through  official  communication  to  the  Investigator.
StudioSoundi
25/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

13.6  Deviations  from  the  clinical  investigation  plan
13.7  Study  monitoring
13.5  Data  processing
13.4  Participant  confidentiality
26/29
Confidential  –  Version  1.0  of  15  Feb  2023
Any  modification  to  the  informed  consent  must  be  approved  by  the  Ethics  Committee.
The  investigator  must  not  deviate  from  the  protocol  unless  necessary  to  eliminate  an  immediate  danger  to  patients  in  the  study.
The  informed  consent  to  the  study,  signed  in  the  original,  must  be  archived  by  the  Investigator  after  having  delivered  a  copy  to  
the  patient.
Before  any  study  procedure,  the  subject  will  express  his  or  her  written  consent  in  a  specific  document  approved  by  the  Ethics  
Committee.
Written  authorization  for  the  same  amount  of  personal  data  will  be  obtained  from  each  subject  before  recruitment  into  the  study  
in  accordance  with  EU  Regulation  2016/679  and  the  applicable  privacy  regulations.  Failure  to  sign  the  consent  to  data  processing  
will  preclude  the  possibility  of  participating  in  the  study.
The  patient  must  be  given  adequate  time  to  reflect  before  signing  the  informed  consent.
The  aim  of  the  monitoring  is  to  verify  that  the  rights  and  well-being  of  patients  are  protected,  that  the  study  data  reported  is  
accurate,  complete  and  verifiable  on  the  basis  of  the  original  data  and  that
Monitoring  of  the  study  will  be  carried  out  by  the  Promoter's  staff.
An  information  sheet  written  in  non-technical  language  and  containing  all  the  most  important  aspects  of  the  study  will  be  given  
to  the  subject  and  he  will  be  given  the  opportunity  to  ask  questions  to  clarify  any  doubts.
It  is  the  Investigator's  responsibility  to  ensure  that  the  confidentiality  of  all  subjects  participating  in  the  study  and  all  their  medical  
information  is  maintained  throughout  the  study.
The  personnel  authorized  by  the  Promoter,  or  the  Ethics  Committee  or  the  Regulatory  Authority  who  will  have  direct  access  to  
the  study  documentation  and  medical  records  of  the  participating  subjects  for  verification  purposes,  will  be  bound  by  the  obligation  
of  confidentiality.
Monitoring  activities  will  be  carried  out  periodically  at  the  center,  according  to  the  monitoring  plan.
The  subjects  will  be  identified  by  a  unique  alphanumeric  code  which  will  be  used  in  CR  and  in  any  other  study  document.  The  
identifying  information  will  be  kept  separate  in  a  secure  location  with  access  limited  to  study  personnel.
Any  deviations  from  the  study  protocol  must  be  notified  to  the  Sponsor,  documented  on  the  appropriate  form  and  communicated  
to  the  Ethics  Committee,  if  required  by  local  regulations.
The  informed  consent  process  will  be  documented  in  the  source  documents.
Any  deviation  from  the  clinical  protocol  will  be  grounds  for  exclusion  of  patients  from  the  study.
StudioSoundi
Machine Translated by Google

13.8  AuditedInspections
15.1  Sourcedocuments
15.  Data  management  and  storage
14.  Ownership  and  Data  Publication  Policy
To  ensure  compliance  with  the  protocol,  study  procedures,  ICH-GCP  and  all  applicable  regulatory  requirements,  the  Sponsor  may  
conduct  an  audit  at  the  participating  centre.
Such  audits/inspections  may  be  carried  out  at  any  time  during  or  after  the  completion  of  the  study.
In  the  event  of  an  audit,  the  Principal  Investigator  and  the  Institution  agree  to  allow  the  auditor/inspector  direct  access  to  all  relevant  
documents  and  to  ensure  that  time  is  available  to  discuss  the  results  of  the  audit/inspection  and  any  findings  in  the  presence  of  the  
Sponsor,  if  required  or  necessary.
The  results  deriving  from  the  clinical  investigation  may  be  the  subject  of  joint  publication  in  the  name  of  the  Promoter  and  the  Principal  
Investigator.  These  results  may  be  published  in  national  and  international  journals  or  presented  at  similar  congresses,  conferences,  
seminars.
regulatory.
The  Regulatory  Authority  may  carry  out  an  inspection  of  the  study.  The  Principal  Investigator  must  promptly  inform  the  Sponsor  if  an  
inspection  by  the  Regulatory  Authority  has  been  scheduled  at  his  site.
The  Investigator  must  give  the  monitors  direct  access  to  the  original  study  documents  (provided  that  the  confidentiality  of  the  subjects  
is  protected)  and  provide  adequate  space  and  time  to  carry  out  monitoring.
the  study  is  conducted  in  accordance  with  the  protocol,  the  study  procedures,  the  ICH-GC  and  the  requirements
Source  documents  are  generally  the  documents  on  which  information  or  data  were  recorded  for  the  first  time  and  may  include  patient  
medical  records,  questionnaires,  as  well  as  diagnostic  test  results.
The  Investigator  is  responsible  for  ensuring  the  reliability,  accuracy,  completeness,  originality  and  readability  of  the  data  reported  in  the  
source  documents.
If  requested,  the  Investigator  will  provide  the  Sponsor  and  the  Regulatory  Authority  with  direct  access  to  the  source  documents.
The  Promoter  is  the  exclusive  owner  of  all  information  arising  from  the  clinical  investigation,  including  resulting  data,  results,  discoveries,  
inventions,  know-how  and  similar.
The  Investigator  must  keep  adequate  and  accurate  documentation  to  allow  the  execution  of  the  study  to  be  fully  documented  and  to  
subsequently  verify  the  clinical  investigation  data.
StudioSoundi
27/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google

If  the  Investigator  wishes  to  transfer  the  clinical  investigation  documents  to  another  location,  he/she  must  inform  the  Sponsor  in  
advance.
The  documentation  of  the  clinical  investigation  must  be  kept  in  a  safe  place  which,  if  necessary,  allows  for  timely  recovery.
The  insurance  coverage  of  the  risks  relating  to  the  study  is  guaranteed  by  an  insurance  policy  stipulated  ad  hoc  
by  the  Promoter  pursuant  to  the  Ministerial  Decree  of  14  July  2009.  The  insurance  coverage  will  be  covered  by  the
Promoter.
The  data  reported  in  the  eCRF  must  be  consistent  with  the  source  documents.  The  eCRF  will  never  be  considered  as  a  source  
document  for  the  study.
The  Investigator  will  have  to  keep  the  documentation  relating  to  this  clinical  investigation  for  at  least  10  years  from  the  conclusion  
or  for  a  longer  period,  if  required  by  the  applicable  legislation.
Center  staff  will  receive  training  in  accessing  the  eCRF  and  entering  data.  Only  designated  and  trained  staff  will  receive  personal  
access  to  the  eCRF.
An  electronic  Case  Report  Form  (eCRF)  will  be  used  in  this  study  to  meet  regulatory  requirements,  ensuring  system  validation,  
traceability  and  audit  trail,  preservation,  protection,  reproducibility  and  recovery  of  experimental  data,  control  of  access  to  
information  and  electronic  signature.
risk/benefit  ratio  for  participating  subjects.
This  study  will  have  a  data  monitoring  steering  committee  which  will  include  representatives  of  the  Promoter  and  the  Principal  
Investigator.  All  study  endpoints,  objectives  and  safety  data  will  be  reviewed  regularly  by  the  steering  committee  which  will  meet  
periodically  in  order  to  carry  out  a  timely  analysis  of  the  tests  progressively  carried  out.  The  steering  committee  will  have  the  
possibility  to  decide  to  suspend  the  investigation  in  case  of  security  problems  and  may
recommend  changes  to  the  investigation,  including  discontinuation,  if  there  is  a  change  in  the
17.  Steering  Committee
16.  Insurance
18.Bibliography
15.3  Document  storage
15.2  CaseReportForm
StudioSoundi
28/29
Confidential  –  Version  1.0  of  15  Feb  2023
248541B1
[2]Marzorati,D.,Bovio,D.,Salito,C.,Mainardi,L.,&Cerveri,P.
(2020).ChestwearableapparatusforcufflesscontinuousbloodpressuremeasurementsbasedonPPGandPCGsignals.  IEEEAccess,8,55424-5
https://worldwide.espacenet.com/patent/search/family/056940255/publication/EP3248541B1?q=pn%3DEP3
[1]PhysilogicalMonitoringDevice
Machine Translated by Google

[5]RossiM.,SalaD.,BovioD,SalitoC.,AlessandrelliG.,LombardC.,MainardiL.,CerveriP.(2022)  SLEEP-SEE-
THROUGH:explainabledeeplearningforsleepeventdetectionandquantificationfromwearablesomnography.  
SubmittedtoIEEEJournalofBiomedicallandHealthInformatics.
[6]LinL.IK(1989)Aconcordancecorrelationcoefficienttoevaluatereproducibility.  Biometrics45:255-268.
[7]AltmanDG,BlandJM(1983).“Measurementsinmedicine:theanalysisofmethodcomparisonstudies”.  
TheStatistician.32(3):307–317.
[8]LandisJR,KochGG.Themeasurementofobserveragreementforcategoricaldata.  Biometrics.1977Mar;33(1):159-74.
[4]Rossi,M.,Alessandrelli,G.,Dombrovschi,A.,Bovio,D.,Salito,C.,Mainardi,L.,&Cerveri,P.(2022).
IdentificationofCharacteristicPointsinMultivariatePhysiologicalSignalsbySensorFusionandMulti-TaskDeepNetworks.  
Sensors,22(7),2684.
IEEETransactionsonBio-medicalEngineering.
[3]Marzorati,D.,Dorizza,A.,Bovio,D.,Salito,C.,Mainardi,L.,  &Cerveri,P.(2022).HybridConvolutionalNetworksforEnd-to-
EndEventDetectioninConcurrentPPGandPCGSignalsAffectedbyMotionArtifacts.
StudioSoundi
29/29
Confidential  –  Version  1.0  of  15  Feb  2023
Machine Translated by Google