Radiofrequency Ablation for Multi-level Obstructive Sleep Apnea: A Single-arm, Multicenter Study
Phase: NA
Conditions: Apnea, Sleep
Sponsor: Olympus Surgical Technologies Europe

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Protocol 990211 RAMOSA 
RFA for multi-level OSA  
Protocol version 6.0 from 26th September 2014 
 
Clinical Study Protocol 
 
 
 
Radiofrequency Ablation for Multi-level Obstructive Sleep Apnea: 
A Single-arm, Multicenter study 
 
 
 
 
 
 
Short Title:  RAMOSA  
Protocol Number:  990211 
Version 6.0 
Date:  September 26, 2014 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
DO NOT COPY 
 
 
 
 
 
 
 
 
This protocol contains confidential information for use only by physicians participating in the 
RAMOSA study.  This document should be maintained in a secure location and should not be 
copied or made available for review by any unauthorized person or firm. 

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Protocol 990211 RAMOSA 
RFA for multi-level OSA  
Protocol version 6.0 from 26th September 2014 
INVESTIGATORS 
 
 
 
 
 
 
2.  
 
3.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SPONSOR 
Olympus Winter & Ibe 
Kuehnstr. 61 
22045 Hamburg 
Germany 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
background
FDA-cleared devices has demonstrated promise as a 
treatment alternative for obstructive sleep apnea in multiple 
published studies. In these studies, repeated RFA of the soft 
palate and base of tongue region resulted in significant 
reductions in AHI and daytime sleepiness without significant 
complications. RFA has several advantages over traditional 
surgical approaches including its ability to address multiple 
levels of the airway (nose, palate, tongue); ability to perform 
in the office under local anesthesia; lower cost; and minimal 
pain and morbidity. The Celon ProSleep plus, the device 
used in this study, was already used in a few studies to treat 
soft palate and base of tongue in OSAS patients. 
Study Justification
Surgery in OSAS is less commonly used for a number of 
reasons foremost of which is the inconsistent success and 
high pain and morbidity of the most commonly performed 
procedure uvulopalatopharyngoplasty (UPPP; removal of 
tonsils and uvula and soft palate tissue). RF ablation of the 
soft palate and base of tongue is considered as a minimal 
invasive treatment method with relative few post-surgery 
complications.  
Inclusion Criteria
x 
Adults ( 22 years) 
x 
Self-report of daytime somnolence 
x 
Body mass index (BMI)  32 
x 
Mild to moderate obstructive sleep apnea (AHI 10-30; 
lowest O2 sat  80%) based on a prior PSG conducted 
within 12 months of enrollment, or based on a 2-night 
home sleep study using the WatchPAT 200S-3. 
x 
Evidence of palate and tongue base collapse on supine 
fiberoptic examination (Müller's maneuver ) 
x 
Have failed or have not tolerated CPAP treatment (see 
Section 5.1 for details) 
x 
No prior surgical treatment for OSAS other than nasal 
surgery or tonsillectomy. 
x 
Willing and capable of providing informed consent 
x 
Willing and capable to return for all follow-up visits and 
PSG sleep-studies and filling out the questionnaires. 
Exclusion Criteria
x 
No regular bed partner 
x 
Another significant sleep disorder (e.g., insomnia, 
periodic limb movement) 
x 
Tonsillar hypertrophy 
x 
Chronic Obstructive Pulmonary Disease (COPD) 
x 
Interstitial Lung Disease (ILD) 
x 
Cystic Fibrosis 
x 
Acute Respiratory Distress Syndrome (ARDS) 
x 
Nasal or supraglottic obstruction on fiberoptic 

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Protocol 990211 RAMOSA 
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examination
x 
ASA class III ,IV, V 
x 
Latex allergy 
x 
Lidocaine allergy 
x 
Pregnancy or plans to become pregnant 
      Note: women of childbearing potential must demonstrate 
a negative pregnancy test upon enrollment; those 
patients qualified to progress to RFA must also 
demonstrate a negative pregnancy test within 7 days 
prior to the date of RFA procedure. 
x 
Major depression or non-stabilized psychiatric disorder 
x 
Drug or alcohol abuse 
x 
Previous palatal or tongue surgery 
x 
Stable or unstable angina 
x 
CHF 
x 
Moderate or severe valvular disease 
x 
TIA/CVA 
x 
Carotid stenosis or endarterectomy 
x 
Anemia 
x 
Room air SpO2 < 95% 
x 
Pulmonary hypertension 
x 
Dialysis 
x 
Central or mixed apnea  10% of respiratory events 
x 
Participation in another clinical study (enrolled in any 
concurrent study) whose investigational plan is judged 
to interfere or affect any of the measures of this study 
Study Endpoints
Effectiveness of the CelonProSleep plus will be assessed by 
demonstrating adequate reduction in AHI and ODI as defined 
below: 
A responder to the CelonProSleep plus RFA treatment is defined 
as a patient with an AHI reduction 50% and a reduction of 
their ODI 25% at the 6-month follow-up PSG, and their AHI at 
the 6-month follow-up is ޒ20. 
# of patients
43 + 10% dropouts (n=48)
Treatment Procedure
Three treatment sessions of RF ablation of the soft palate (7 
lesions) and the base of tongue (6 lesions). 
Statistical Analysis of 
Endpoints 
The performance endpoints will be assessed by recording the 
functional parameters and by monitoring the patient clinical 
status. Safety assessments will consist of recording of any 
adverse events. Variables will be analyzed by using appropriate 
statistical techniques for parametric and continuous 
measurements. 
Follow-up
6 months after the last RFA treatment. 
Study Duration 
24 weeks plus 6 months of follow-up for each patient

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Protocol version 6.0 from 26th September 2014 
Table of Contents 
 
 
1.   BACKGROUND………………………………………………………………….. .9 
1.1   Obstructive Sleep Apnea…………………………………………………………….9 
1.2  
Diagnosis of Obstructive Sleep Apnea…………………………………………….. .9 
1.3   Surgical Therapy for OSA…………………………………………………………..10 
1.4  
CelonProSleep plus………………………………………………………………… 11 
1.5  
Safety of RF ablation of the soft palate and base of tongue……………………… 12 
 
2.      STUDY DESIGN……………………………………………………………………..17 
 
2.1 
Study Type…………………………………………………………………………. 17 
2.2 
Scale………………………………………………………………………………... 17 
2.3 
Duration……………………………………………………………………………. 17 
2.4   Study objectives…………………………………………………………………......17 
2.5  
Determination of last Follow-up visit……………………………………………… 18 
 
3.      HYPOTHESES AND DATA ANALYSIS……………………………………….....19 
 
3.1 
Primary Efficacy Endpoints………………………………………………………... 19 
3.1.1   Experimental Design……………………………………………………………….. 20 
3.1.2 Subjects included in the Primary Efficacy Objective Analysis……………………. 20 
3.1.3 Hypotheses…………………………………………………………………………. 20 
3.2 
Sample Size Rational………………………………………………………………. 21 
3.3   Secondary Efficacy Endpoints…………………………………………………….. 21 
3.3.1 Experimental Design……………………………………………………………….. 21 
3.4   Secondary Endpoints………………………………………………………………. 22 
3.4.1   Functional Outcomes Sleep Questionnaire (FOSQ)……………………………….. 22 
3.4.1.1 Description and Rational……………………………………………………………22 
3.4.1.2 Objective and Hypotheses…………………………………………………………..22 
3.4.2   Epworth Sleepiness Scale (ESS)…………………………………………………… 22 
3.4.2.1 Description and Rationale………………………………………………………….. 22 
3.4.2.2 Objective and Hypotheses…………………………………………………………. 23 
3.4.3   Visual Analog Scale (VAS)………………………………………………………... 23 
3.4.3.1 Description and Rationale………………………………………………………….. 23 
3.4.3.2 Objective and Hypotheses…………………………………………………………. 23 
3.4.4   Percentage Sleep Time at SaO2 < 90%..................................................................... 23 
3.4.4.1 Description and Rationale………………………………………………………….. 23 
3.4.4.2 Objective and Hypotheses…………………………………………………………..23 
3.5   
Safety and tolerability of RFA treatment…..………………………………………. 24 
3.6  
Ancillary Data Collection………………………………………………………….. 24 
 
4.      RESEARCH DESIGN……………………………………………………………… 25 

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4.1.1  Inclusion Criteria………….……………………………………………………….. 25 
4.1.2   Exclusion Criteria………………………………………………………………….. 25 
4.2 
Sampling Methods…………………………………………………………………..26 
 
5.      PROCEDURES DURING THE STUDY…………………………………………. 27 
 
5.1     Visit 1- Screening Visit and home Sleep Study……………………………………. 27 
5.2     Visit 2 - Baseline visit and PSG sleep study……………………………………… 27 
5.3     Visit 3- Stage I: First Radiofrequency Treatment (within 2 weeks of screening)…. 28 
5.4     Visit 4 - Stage II: Second Radiofrequency Treatment (6 weeks later)…………….. 31 
5.5     Visit 5- Stage III: Third Radiofrequency Treatment (6 weeks later)………………. 32 
5.6     Visit 6- Follow-Up Visit (6 weeks later)………………………………………….. 32 
5.7     Visit 7- Final Follow-up Visit (6 months later)………………………………….. 32 
5.8     Visit 8 - Final Study Visit…………………………………………………………. 33  
 
6.         DURATION………………………………………………………………………...33 
7.         INSTRUMENTS………………………………………………………………….. 33 
8.         STATISTICAL ANALYSIS………………………………………………………34 
 
8.1 
Primary Efficacy Endpoint………………………………………………………… 34 
8.2 
Additional analysis…………………………………………………………………. 35 
8.3 
Calculations of Statistical power………………………………………………….. 35 
8.4 
Analysis Sets………………………………………………………………………. 36 
8.5 
Handling of Missing Data, Subject Withdrawals, and Treatment Failures……….. 36 
8.6 
Interim Analyses…………………………………………………………………... 36 
 
9.         RISK ANALYSIS………………………………………………………………… 37 
 
9.1  
Risks of Confidentiality…………………………………………………………… 37 
9.2   Risks and Discomforts …………………………………………………………….. 37 
9.3  
Minimization of Risk to the Patient………………………………………………... 38 
9.4  
Potential Benefits…………………………………………………………………... 38 
 
10        ADVERSE EVENT MANAGEMENT………………………………………….. 39 
 
10.1  Definitions…………………………………………………………………………..39 
10.1.1  Adverse Event (AE)…………………………………………………………………39 
10.1.2  Adverse Device Effect (ADE)……………………………………………………....39 
10.1.3  Serious Adverse Event (SAE)……………………………………………………… 39 
10.1.4 Serious Adverse Device Effect (SADE)…………………………………………… 40 
10.1.5 Relatedness………………………………………………………………………… 40 
10.1.5.1   Surgical Procedure Related……………………………………………………… 40 

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10.1.5.2   Other Surgical Procedure Related………………………………………………. 40 
10.1.5.3   Pre-existing or Independent Condition Related…………………………………. 40 
10.1.5.4   Other…………………………………………………………………………….. 40 
10.2    AE Definitions for Sponsor Classification………………………………………. 41 
10.2.1    Unanticipated Adverse Device Effect (UADE)………………………………….. 41 
10.2.2    System component-relatedness…………………………………………………... 41 
10.3    Adverse Event Adjudication……………………………………………………... 41 
10.4    Adverse Event Outcome Status………………………………………………….. 41 
10.5     Notification of Serious Adverse Events…………………………………………. 41 
10.6        Subject Deaths…………………………………………………………………… 42 
 
11.     PROTOCOL DEVIATIONS/MODIFICATION………………………………….42 
 
12.     DATA QUALITY ASSURANCE…………………………………………………. 43 
 
12.1  Required Data……………………………………………………………………… 43 
12.2  Monitoring Procedures…………………………………………………………….. 43 
12.3  Patient Data Protection…………………………………………………………….. 44 
12.4  Ethical and Regulatory Considerations……………………………………………. 44 
 
13.     ROLES AND RESPONSIBILITIES……………………………………………… 44 
 
13.1  Role of the Sponsor Representatives ……………………………………………… 44 
13.2  Investigator’s Role and Responsibilities…………………………………………… 45 
13.2.1 Clinical Investigators………………………………………………………………. 45 
13.2.2 Investigator Selection………………………………………………………………. 46  
13.3 
Study Initiation…………………………………………………………………….. 46  
13.4 
Clinical Events Committee (CEC)………………………………………………… 46 
13.5  Patient Informed Consent………………………………………………………….. 46 
13.6  Study Termination…………………………………………………………………. 46 
13.7  Withdrawal…………………………………………………………………………. 47 
13.8  Protocol Deviations………………………………………………………………… 47 
13.9  Stopping Rules…………………………………………………………………….. 47 
 
14.      REFERENCES……………………………………………………………………. 48 
 
APPENDIX I – TIME TABLE……………………………………………………………52 
 
 
 
 
 
 
 
 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
1. 
BACKGROUND 
 
1.1 
Obstructive Sleep Apnea 
 
The United States is currently experiencing an increase in the incidence and prevalence of obstructive 
sleep apnea (OSA). With prevalence in middle-aged adults of 2 to 4% of the population, untreated OSA 
increases the risk for cardiovascular disease, including hypertension and heart failure, daytime 
sleepiness, and increased risk of motor vehicle accidents1-6. 
 
Despite its prevalence and increased recognition as a cardiovascular risk factor, OSA remains largely 
under diagnosed. The standard test for diagnosis of OSA is polysomnography (PSG), which produces 
outputs on a number of physiological variables. The apnea-hypopnea index (AHI), expressed as the 
number of apneas/hypopneas per hour of sleep, is the most commonly used variable to measure the 
severity of disease. Generally speaking, an AHI of 5 or greater when associated with daytime 
sleepiness connotes a diagnosis of sleep apnea. An AHI between 5 and 14 is defined as mild disease, 
whereas an AHI of 15 to 30 is moderate, and an AHI greater than 30 is severe disease. The goal of 
treatment of OSA is improvement of AHI and other key variables (such as lowest oxygen saturation, 
LSAT), and improvement of patient symptoms and reduced cardiovascular and overall mortality. 
 
The first line and most common treatment for OSA is continuous positive airway pressure (CPAP), 
utilized by an estimated 3 million Americans. CPAP is effective in reducing the AHI if used properly. 
However, the nasal and/or facial mask required for CPAP during sleep may lead to poor adherence to 
therapy. Published studies on CPAP have shown that only 58 to 80% of patients accept CPAP therapy7-
10, with 65 to 90% exhibiting long-term adherence to CPAP, therefore 10-40% of patients fail to 
maintain CPAP use over time11. Additionally, many patients treated successfully with CPAP have low 
treatment satisfaction due to facial discomfort, nasal blockage, abdominal bloating, and loss of 
intimacy with their bed partner. CPAP variations such as auto-titrating CPAP, heated and humidified 
air, and bi-PAP (different pressures on inspiration and expiration) have failed to consistently improve 
patient adherence to therapy, indicating a significant unmet need for CPAP alternatives in patients who 
are not adherent to therapy12. 
 
1.2 
Diagnosis of Obstructive Sleep Apnea 
 
The gold standard for the diagnosis of OSA remains the attended overnight level I polysomnogram 
(PSG). PSG’s include electroencephalogram (EEG), electro-oculogram (EOG), electromyogram 
(EMG), electrocardiogram (ECG), oronasal airflow, thoracic and abdominal movement, oxygen 
saturation, snoring level, and body position13.  However, PSG has many limitations including high cost, 
long waiting lists, limited availability and the need for technical expertise to perform and interpret. In 
addition, many patients find the PSG equipment too cumbersome and may be reluctant to spend the 
night in the laboratory. Thus, it is not possible to perform PSG studies for all individuals suspected of 
having OSAS and waiting duration for PSG may exceed months to years18, resulting in patients who 
are waiting long time for an adequate therapy.  
 
As a result of these factors single and multiple channel monitoring systems have been introduced to 
screen for OSA. One of these systems is the WatchPAT 200S-3 (Itamar Medical Inc., Franklin, MA, 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
USA)1, which  is a level III (minimum of 4 physiologic channels) portable diagnostic sleep device that 
is worn on a patient’s wrist along with two self-adhesive finger probes. The device measures several 
parameters including pulse Oximetry, heart rate, wrist actigraphy (muscle twitches), body position, 
snoring, and peripheral arterial tonometry (PAT). The WatchPAT 200S-3 uses patented algorithms 
which interpret the physiologic measurements to detect the presence of sleep-disordered breathing. A 
major advantage to the system is its ease of use which can be easily applied by the patients in the 
comfort of their own bedroom, an environment that best reflects the pattern of their sleep habits. 
Increasingly, the public and third-party payers are requiring home sleep testing devices such as 
WatchPAT as the initial diagnostic for sleep-disordered breathing due to increased patient acceptance 
and reduced cost of care.  
 
In 2007, the AASM published its clinical guidelines for the use of unattended portable monitors in the 
diagnosis of OSA in adult patients16. These guidelines state that “ the Portable Monitoring Task Force 
of the American Academy of Sleep Medicine (AASM) makes the following recommendations: 
unattended portable monitoring (PM) for the diagnosis of obstructive sleep apnea (OSA) should be 
performed only in conjunction with a comprehensive sleep evaluation. On December 14, 2007 the 
CMS released its proposed decision for modification of NCD policy 240.41 pertaining to coverage of 
CPAP therapy for adult obstructive sleep apnea (OSA). The proposed modification allows for an initial 
12 week period of CPAP coverage when OSA is diagnosed using both a clinical evaluation and PSG 
performed in the sleep laboratory or a clinical evaluation and unattended home sleep studies using a 
Type II, III or IV device17. 
 
With WatchPAT 200S-3, both RDI and AHI scores are highly reproducible, showing correlation 
between home and in-laboratory sleep studiese.g.19-24. This study will utilize WatchPAT 200S-3 for 
screening of the qualification of the patient to participate in the study regarding his/her AHI score. In 
addition, patients will undergo WatchPAT home sleep study at both follow-up visits for determining 
changes compared to the screening visit. In order to decrease the risk of overestimation of OSA 
variables with increasing severity of OSA the current study will include only mild to moderate patients. 
 
1.3 
Surgical Therapy for OSA 
 
Surgical therapy for OSA is less common than CPAP therapy. Fewer than 100,000 surgical treatments 
for OSA are performed in the United States annually, despite the fact that up to a third (700,000) of the 
two million people in the U.S. who start CPAP each year may ultimately fail to adhere to CPAP over 
the long-term. Surgery is less commonly used for a number of reasons foremost of which is the 
inconsistent success and high pain and morbidity of the most commonly performed procedure 
uvulopalatopharyngoplasty (UPPP; removal of tonsils and uvula and soft palate tissue). The most 
effective surgeries for OSA require multi-level treatment (palate and tongue base levels), are more 
complex, and are not as widely available since they require specialized surgical training and experience 
that are not generally available. In the literature, a successful surgical treatment is generally defined as 
a 50% reduction in AHI and an overall post-treatment AHI of < 20/hour25. 
 
                                              
1 510(k) premarket notification numbers K102567, K042916, K010739 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
Surgical therapy is based in part on an anatomic assessment of the likely sites of obstruction.  Anatomic 
analysis is most commonly performed with fiberoptic examination of the upper airway, with 
radiographic imaging reserved for cases of suspected craniofacial abnormality. Under the classification 
of Fujita,26,27 patients with obstruction in the oropharynx only are considered type I; those with 
obstruction in the oropharynx and the hypopharynx are considered type II (mixed site of obstruction); 
while those with hypopharyngeal-only obstruction are considered type III. Most patients (>75%) have a 
mixed site of obstruction (type II)28. Multilevel obstruction is a common denominator for many patients 
with OSA, whether it is classified as mild, moderate, or severe disease29-33. Therefore, surgical 
treatments must be multi-level by necessity in order to address potential sites of obstruction. Whereas 
unselected single site surgery of the oropharynx (soft palate) with uvulopalatopharyngoplasty (UPPP) 
is successful only 40% of the time, surgical success can be improved to greater than 65% when UPPP 
is combined with procedures to address the base of tongue (hypopharynx). This 65% success rate of 
multi-level sleep surgery approaches the long-term adherence and success rate of CPAP therapy25. 
 
Radiofrequency ablation (RFA) of the upper airway using FDA-cleared devices has demonstrated 
promise as a treatment alternative for obstructive sleep apnea in multiple published studies 29-31, 34. In 
these studies, repeated RFA of the soft palate and base of tongue region resulted in significant 
reductions in AHI and daytime sleepiness without significant complications. RFA has several 
advantages over traditional surgical approaches including its ability to address multiple levels of the 
airway (nose, palate, tongue); ability to perform in the office under local anesthesia; lower cost; and 
minimal pain and morbidity.  
 
RFA enables the surgeon to direct the delivery of a specific amount of radiofrequency energy, 
measured in joules, to a specific site at a controlled temperature. This radiofrequency energy is 
delivered at relatively low power and voltage. Application of radiofrequency energy in this manner 
causes tissue ions to become agitated due to changes in electrical flow inherent in alternating current. 
These ionic shifts result in resistive heating by the tissue itself, and in comparison to electrocautery, the 
production of low temperatures (60° to 95°C). Protein, which denatures at temperatures in excess of 
47°C, undergoes tissue coagulation along with surrounding stromal and vascular tissue. The lesion 
created by RFA is consistent with tissue coagulation and results in congestion, edema, and an acute 
inflammatory response within the first 24 hours. Over a period of 72 hours, the treated area progresses 
to tissue necrosis which may change to fibrotic tissue over the course of 10 days. 
 
Volumetric reduction occurs in 2 stages. The contracted area of fibrosis occupies a smaller area than 
normal tissue and retracts the surrounding normal tissue resulting in the first stage of volumetric 
reduction of tissue. The second stage, resulting in further volumetric reduction, occurs over the course 
of several months as the body resorbs the area of fibrosis. 
 
The CelonProSleep plus, the device used in this study, is a FDA-cleared RFA device (K032838) 
that is indicated for ablation and coagulation of soft tissue in otorhinolaryngology (ENT) surgery 
including submucosal tissue shrinkage and tissue coagulation in the uvula/soft palate for the 
treatment of snoring. The system is intended for use by qualified medical personnel trained in the use 
of electrosurgical equipment. 
 
 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
1.4 
CelonProSleep plus 
 
The CelonProSleep plus is a rigid, sterile, single-use, bipolar electrosurgical electrode.  It is used in 
conjunction with the electrosurgical generator CelonLab ENT. The device is indicated for the ablation 
and coagulation of soft tissue in otorhinolaryngology surgery including submucosal tissue shrinkage 
and tissue coagulation in the uvula/soft palate for the treatment of snoring, and the soft palate 
(velopharynx) and base of tongue (oropharynx) for the treatment of mild to moderate obstructive sleep 
apnea syndrome (OSAS). 
 
Two electrodes located coaxially on the distal end of the device allow the generator to deliver a bipolar 
output to the tissue area, thus a neutral electrode or return conductor is not required. This is an 
advantage over other approved radiofrequency devices (ex. Somnoplasty) that require placement of a 
grounding pad on the patient and could interfere with implantable pacemakers. The power output on 
the device is controlled by the user on the generator unit. During its operation, tissue impedance is 
measured as coagulation status feedback. An acoustic signal from the generator unit informs the user 
that the coagulation process is complete and results in the automatic cessation of output power, 
ensuring safety in operation.   
 
The dimensions of the CelonProSleep plus is designed for otorhinolaryngology surgeries—the bend 
angle and electrode length allow placement of electrode tip on the target tissue areas in the oral cavity 
and the trocar tip is appropriate for ablation and coagulation of tissues that are difficult to penetrate.  
 
                                                  Fig. 1 The CelonProSleep plus  
 
Each electrode is supplied with an insulating cover that allowed exposure of only 1 cm of active 
electrode to avoid mucosal injury during treatment. The application time varied between four to six 
seconds per puncture (soft palate) and ten to sixteen seconds at the base of tongue, terminated by 
acoustic ‘end-indication’ and auto-stop facilitated by a thermistor and tissue impedance measurement at 
the probe tip. Energy delivery can be manually terminated by the operator if any pain or blanching of 
mucosa occurred.  
 
 

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Protocol version 6.0 from 26th September 2014 
1.5 
Safety of RF ablation of the soft palate and base of tongue 
 
Radiofrequency ablation of the soft palate and base of tongue is considered as a minimally invasive 
therapy with much less side effects and complications in comparison to other surgical therapies for 
OSAS39, 40. 
 
Potential specific complications of radiofrequency ablation include bleeding, infection, ulceration, 
palatal fistula, tongue weakness, and taste disturbance alongside globus sensation. Long-term 
complications are unusual but globus sensation may persist in up to 10 % of patients. Most patients 
recover quickly however and report improvements in snoring although a recent systematic review 
indicated that further long-term studies are required41-43.  
 
In a retrospective study, 130 patients underwent one to three sessions of RFA of soft palate (6 lesions) 
and base of tongue (6 lesions) with either Somnus (Gyros-ENT), or the CelonProSleep plus (Caroll et 
al. 32, with 
the PI in this study). The most common complication of upper airway RFA 
was mucosal ulceration (11%; mild side effect45), which healed with saline gargles within 10 days to 2 
weeks. Ten patients (8%) had significant palatal or tongue edema (mild complication), which interfered 
with speech and/or swallowing but resolved within a few days of starting a taper dose of steroids. One 
patient had a temporary paresis of the lingual nerve (moderate complication), which resolved a couple 
of weeks after tongue base RFA. This was attributed to a pressure neuropathy from the laryngoscope 
because the lingual nerve was not within the field of the RFA application. No patient had a severe or 
prolonged dysphagia preventing oral diet immediately after the procedure. However, no information is 
given whether the complications caused by using the Somnus or the CelonProSleep plus32. 
 
Factors that affect RFA complications may be repeated RFA treatment to the same tissue, learning 
curve of individual surgeons, energy delivered per lesion, temperature selection, anatomical site 
treated, and perioperative steroid use45. 
 
Kezirian et al.45 reported incidence of complications after RF treatment of the soft palate and base of 
tongue. 22 publications on the soft palate with a total number of patients of 669 and 1406 RF treatment 
sessions were reviewed. The total number of complications was 119 (0.6%), with 111 minor, 7 
moderate, and 1 major complication. Of the reviewed studies only one study used the CelonProSleep 
plus67 (Tatla et al., 2003: 10 patients, 20 treatment sessions, 120 lesions, 2 mild palatal swelling, 
mucosal ulceration in one lesion).  
 
The review of 9 studies revealed an incidence of complications for the treatment of the base of tongue 
of 48 (2.7%). The number of patients in these studies was 614, and the number of treatment sessions 
was 1392. There were 10 minor, 28 moderate, and 10 major complications. None of these studies used 
the CelonProSleep plus RF device45. 
 
Farrar et al., (2008, with 
 PI)35 conducted a meta-analysis on published studies to obtain 
a precise estimate to the effectiveness of RFA in the treatment of OSA. The total number of soft palate 
complications was 13 (3.9% in 144 patients over 331 treatments sessions), and the total number of base 
of tongue complications was 38 (3.5% in 252 patients over 1092 treatment sessions). Out of 16 studies 

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only one study used the CelonProSleep plus for RFA treatment of the base of tongue (den Herder46: 24 
patients, 1-3 treatment sessions, 6 lesions/session, no complications).  
 
A compendium of published studies on RFA of the soft palate and base of tongue is presented in Table 
1. 
 
Table 1    
Author 
(yr) 
Sample 
Size 
Sites 
Treated 
# of 
Lesions 
BOT/SP 
per 
session 
# RF 
Sessions 
Interval 
between 
Treatments 
# 
Complications 
 / n patients 
Mean 
Follow-
up 
RF Device 
Mean 
Joules 
Power 
Powel 
(1999)47 
18 
BOT 
3-5 
2-9 
3-4 wks 
One patient 
pain on 
swallowing, 1 
patient BOT 
infection 
4 mos 
Somnus 
1543 
J/session 
10 W 
Nelson 
(2001)
48 
10 
BOT 
2-6 
3 
3-6 wks 
None 
Up to 2 
mos 
Somnus 
1,000 
J/lesion 
12,000J/ 
patient 
10 W 
Woodson 
(2001)
49 
56 
BOT 
2-11 
3 
3-4 wks 
25% mild 
edema, 6.2% 
moderate 
(mucosal 
erosion)   
3 mos 
 
Sumnopla
sty 
2,720 
J/session 
10 W 
Stuck 
(2002)50 
18 
BOT 
4 
3.4 
4-6 wks 
Mild to 
moderate 
tongue 
swelling, 
One BOT 
infection 
3 mos 
Sumnos 
2800/sessio
n 
10 W 
Terris 
(2002)51 
10 
SP 
3 
3 
NA 
NA 
4 mos 
Sumnos 
1090/sessio
n 
10 W 
Blumen 
(2002)
56 
29 
SP 
3-4 SP 
2-3 
6-8 wks 
3/29 
4 mos 
Somnus 
2067 
10 W 
Li (2002)52 
16 
BOT 
NA 
5.5 
NA 
NA 
24 mos 
Somnus 
1543 
J/session 
10 W 
Fisher 
(2003)
53 
15 
BOT/SP 
3 BOT 
5 SP 
1 
 
1 session 
1 SP ulceration 
3 mos 
Somnus 
9750 
10 W 
Woodson 
(2003)
29 
26 
BOT/SP 
3 BOT 
3 SP 
5 BOT 
2 SP 
4 wks 
Hematomas 
2.3% 
Ulcerations 
0.8% 
Infections 0% 
NA 
Gyros ENT 
3000 
BOT/session 
1000 
SP/session 
10 W 
Riley 
(2003)31 
20 
BOT 
3 
5 
4 wks 
NONE 
3 mos 
Gyros ENT 
 
10 W 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
7915 Total 
Steward 
(2004)
30 
26 
BOT/SP 
3-4 BOT 
3 SP 
3-5 BOT   
1-3 SP 
3-4 wks 
BOT  
2 hematomas,  
3 ulceration  
SP 
3 Ulceration  
3 mos 
Gyros ENT 
BOT 
1000/sessio
n SP 
1000/sessio
n 
10 W 
Steward 
(2004/1)54 
22 
BOT/SP 
5 BOT 
2 SP 
4.8 BOT 
1.5 SP 
4 wks 
3 hematomas, 
1 mucosal 
ulceration,  
3.1% 
2 to 3 
mos 
Gyros-
ENT 
9500 BOT 
2350 SP 
10 W 
Stuck 
(2004)55 
18 
BOT/SP 
4 BOT 
3-4 SP 
4 BOT  
3 SP 
4-6 wks 
None 
Up to 1 
mos 
Somnus 
2800 BOT 
1800 SP 
10 W 
Steward 
(2005)
34 
29 
BOT/SP 
1-3 BOT 
3 SP 
2-3 BOT/ 
SP 
NA 
None 
23 mos 
Gyros-
ENT 
Up to 3300 
BOT/session 
1300 
SP/session 
10 W 
Blumen 
(2006)68 
10 
BOT 
3-6 
2-3 
4 mos 
1 pt severe 
pain, one pt 
hemilingual 
hypesthesia, 
one pt mild 
swelling 
4 mos 
Somnus 
14,288 J 
15 W 
Holmlund 
(2014)
57 
20 
SF 
3 SP 
3 
4-6 wks 
None 
12 mos 
Coblator 
(arthocare) 
________ 
 
Fernandez-
Julian 
(2009)
58 
29 
BOT 
4  
3 
4-5 wks 
1 patient 
(mucosal 
ulceration) 
0.75 
month 
Somnopla
sty 
3,000 J 
BOT/session 
10 W 
Ceylan 
(2009)33 
47 
BOT/SP 
10 BOT 
3 SP 
1 
___ 
None 
12 mos 
Gyrus-
ENT 
3,000 J BOT 
1,300 J SP 
10 W 
Friedman 
(2007)
59 
122 
BOT 
10 
1 
___ 
1 patient, 
mucosal 
ulceration 
At least 
6 mos 
Gyros-
ENT 
3,000 J BOT 
10 W 
Hultcrantz 
(2010)
60 
29 
SP 
6-8 SP 
4 
NA 
5 patients with 
small ulcers 
40 mos 
Elman 
Surgitrone 
NA 
 
Verse 
(2006)39 
60 
BOT 
4 
4 
4-6 wks 
NA 
8 wks 
Somnus 
 
10 W 
Pazos 
(2001)
61 
30 
BOT/ 
SP 
NA 
2 BOT 
2SP 
6 wks 
11 mild 
6 moderate 
4 severe 
1 
month 
Somnus 
S2 
1,500 J BOT 
1,550 J SP 
10 W 
Den 
Herder 
(2006)
46 
73 
BOT/ 
SP 
6 
1-3 
6 wks 
2 pts with 
tongue 
deviation, 
resolved within 
an hour 
Up to 
1.5 
mos 
CelonLab 
and Celon 
ProSleep 
84 J X 6 
lesions = 
504 Joules  
 
Balsevicius 
(2013)62 
32 
SP 
9 SP 
NA 
6-8 wks 
6 patients 
mucosal 
blanching 
2-3 
mos 
CelonLab 
and Celon 
ProSleep 
 
10 W 

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Protocol 990211 RAMOSA 
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(resolved in 1 
month) 
Civelek 
(2010)
63 
12 
BOT 
5-7 
1 
___ 
None 
 
CelonLab 
and Celon 
ProSleep 
224 J 
 
Van den 
Broek 
(2008)64 
37 
BOT 
6 
1 
___ 
No major 
complications, 
1 pt edema 
 
CelonLab 
and Celon 
ProSleep 
252 J 
7 W 
Heywood 
(2010)
65 
5 
BOT/SP 
6 BOT 
SP NA 
1 
___ 
None 
 
CelonLab 
and Celon 
ProSleep 
240 J/BOT 
SP NA 
6 W 
/BOT 
10 W/ 
SP 
Olszewska 
(2012)66 
79 
BOT 
8-16  
2 
NA 
None 
6 mos 
CelonLab 
and Celo      
n 
ProSleep 
480-960 
J/session 
6 W 
Caroll (& 
Gillespie, 
2012)
32 
130 
 
BOT/SP 
6 BOT 
6 SP 
1-3 
6 wks 
See description 
above 
5 mos 
CelonLab 
and Celon 
ProSleep 
and 
Somnus 
Values are 
given for the 
Somnus 
1800 J 
BOT/ses 
1800 J 
SP/session 
 
Tatla 
(2003)67 
10 
SP 
6 SP 
2 
6 wks 
2 mild palatal 
swelling, one 
lesion mucosal 
ulceration 
1.5 
mos 
CelonLab 
and Celon 
ProSleep 
and 
Somnus 
360 J SP 
/session 
10 W 
 
Eight studies describe the use of the CelonProSleep plus for the RF treatment of the soft palate and 
base of tongue32, 46, 62-67. In seven of these studies there were 199 patients, and the number of lesions 
varied between 6 and 18 for the base of tongue, and 6 to 9 for the soft palate. The number of lesions 
among all studies was approximately a minimum of 2,400 (# of patient * # lesions * one session). 
There were 9 mild complications (0.37%, mucosal blanching), and one moderate complication (0.04%, 
tongue edema). Details on the eighth study, Caroll et al.32, and the number of complications are given 
above. 
 
One of the factors that affect RFA complications is the amount of energy delivered per lesion45. A 
comparison between the studies in the above Table reveals that, the amount of applied energy by using 
the CelonProSleep plus RF device is much less than by using the Gyrus or Somnus devices. For one 
lesion in the base of tongue Gyrus/Somnus recommend target energy of 750 Joules (J). Celon 
recommends using a setting power of 7 W that due to the impedance-feedback auto-stop function 
results in an application time of 7.4 seconds. The applied energy with Celon RF device is E = P * t = 7 
W * 7.4 s = 51.8 Joules. Thus, CelonProSleep plus applies only 51.8 J/lesion compared to the 750 
J/lesion of Gyrus or Somnus.  
 
The Somnus device has a higher energy input and is monopolar, exposing the entire body of the 
patient, whereas the CelonProSleep plus unit has inherent innovative bipolar tip safety. This ensures 
that only tissue in the immediate vicinity of the probe tip, which has a bipolar arrangement of 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
electrodes in the needle, is exposed to the radiofrequency current. This removes some of the risks 
linked to the process and the need for a neutral electrode is lost, eliminating the risk of burns. Further 
safety is provided by acoustic feedback and an auto-stop power control, whereas the Somnus device 
relies on the operator visualizing the temperature and impedance signal.  
 
Due to the bipolar electrode the CelonProSleep plus device coagulates much faster (although the power 
setting  is  less)  than  the  Gyrus  or  Somnos  systems.  Therefore,  less  energy  is  needed  to  reach  the  
coagulation threshold of the tissue. In the case of a very slow coagulation process, as happens with the 
Gyrus or Somnos devices, a big proportion of energy is transported away from the target region by 
circulating blood before the coagulation threshold is reached. 
 
 
2 
STUDY DESIGN 
 
2.1 
Study Type 
 
The RAMOSA Trial is a multi-center, prospective, controlled trial. Sub-studies are not permitted 
without the prior approval of Sponsor. 
 
2.2 
Scale 
 
The study will be conducted at a maximum of 3 centers in which at least one study center will be in the 
United States. Patients will be enrolled to provide data from up to 48 subjects. Data from 43 subjects is 
required to demonstrate efficacy and we count 10% for dropouts (Section 3.2 Sample Size Rational). 
When the treatment limit of 48 subjects is reached, Sponsor may opt to submit for expanded access.   
 
2.3 
Duration 
 
The duration of the RAMOSA trial is expected to be approximately 24 weeks, and follow-up data will 
continue to be collected for 6 months post-treatment. Enrollment in the RAMOSA trial is anticipated to 
require approximately 1 year from the first regulatory authority approval. Once 48 subjects have been 
followed for 24 weeks, the clinical data will be reported to regulatory authorities. All subjects enrolled 
in this study must be followed according to the investigational plan unless Sponsor notifies the 
Investigator to the contrary, or Sponsor has officially closed the study.   
 
2.4   Rational for patient selection 
 
This study aims to evaluate the CelonProSleep plus for multi-level radiofrequency ablation (RFA) of 
the palate and base of tongue as a treatment for mild to moderate obstructive sleep apnea syndrome 
(OSAS) in patients with AHI of 10-30 and BMI  32. The AHI cut-off of 30 is used because patients 
with AHI > 30 have OSA of such severity that they are unlikely to respond to RFA. Unlike traditional 
sleep surgery, RFA does not involve radical removal of tissue but works primarily by remodeling and 
stiffening the tissues of the upper aerodigestive tract. A meta-analysis of RFA studies found a mean 
AHI reduction of 45% after 24-month follow-up35. Since standard measures of surgical success (AHI 
reduced by 50% ) are applied in this study, we anticipate that many patients with severe (AHI >30) 

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Protocol 990211 RAMOSA 
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apnea would not be considered a surgical success and should therefore be excluded in favor of other 
more effective therapy for severe OSA (CPAP or traditional surgery). RFA demonstrates improved 
sleep outcomes if the procedure is repeated on several occasions in order to deliver enough energy to 
create the critical mass of scar tissue to offset the increased collapsibility of the upper airway32, 35. 
Therefore, the present trial will repeat upper airway RFA on three occasions in order to maximize 
treatment effect. The treatment sessions are separated by six weeks since it takes approximately 3-4 
weeks for the lesion to convert to scar and therefore all tissues should be healed by week 636. In 
addition, multiple studies have found that rates of surgical success for OSA decline with increasing 
patient BMI. This is especially true for patients with morbid obesity (BMI >40) who have a significant 
level of lingual and parapharyngeal fat which increase the collapsibility of the upper airway. Since 
most patients with OSA are overweight to obese, too low of a BMI cutoff may be overly restrictive37. 
The BMI cut-off of 32 is a convenient rule-of-thumb frequently used by sleep surgeons which captures 
a large percentage of the OSA population which are more likely to succeed with sleep surgery while 
excluding the most obese subset who are less likely to succeed and are at increased risk for surgical 
complications.     
 
2.5 
Determination of last Follow-up visit 
 
Although in-laboratory PSG is the gold standard for diagnosing OSAS, there are a few factors that may 
lead to biased results when using PSG for determining treatment success in studies that apply long-term 
follow-up measurements (e.g. one year). Some of these factors are 1) selecting only patients that are 
willing to participate in a PSG study might lead to a selection bias and thus, excluding patients who are 
suited for the tested treatment, but are not willing to participate in a PSG study; 2) a long-term follow-
up may lead to a high number of dropouts because of various reasons as described below; and 3) PSG 
records biophysiological changes during sleep, but not the changes occurred in daily life situation from 
the last treatment till the follow-up visit (e.g. change in personal or professional status, weight changes, 
or other factors that are not related to the treatment, but contributing to sleep quality). Thus, a longer 
interval between the treatments to the final follow-up visit will result in an increase in missing data, 
weaken the association between treatment and effect, and potentially introduce bias into the study.  
 
An analysis of the (prospective) RFA studies that are discussed in section 1.5 (Table 1), reveals 
correlative relations between the amount of dropouts and the interval between last RFA treatment and 
the follow-up visit. 12 of these studies had a follow-up visit of up to 4 months29, 31, 39, 46, 48, 50, 53-55, 58, 62, 
67. The mean dropout in these studies was 9,7%, in compared to 24,7% in studies with follow-up of up 
to 12 months (7 studies30, 47, 51, 56, 59, 68, 69) and 24% in studies in which the follow-up was conducted 
within 24 months (2 studies34, 52).   
 
Out of the 22 reviewed studies only two studies reflect on the problem of keeping a study population 
for long-term follow-ups (e.g. 12 months,)). Steward et al. (2005)34, aimed to conduct a long term 
follow-up with patients treated with RFA (one year, home sleep-study). To this end, all potentially 
eligible subjects from a parent trial were offered inclusion in the study. Twenty nine of 46 potentially 
eligible subjects agreed to participate (63%). Of those 17 potentially eligible subjects who did not 
participate (37%), 5 could not be located (moved or bad phone number), 4 refused, and 8 reported that 
they were too busy or missed scheduled appointments and didn’t follow-up despite multiple phone 

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Protocol 990211 RAMOSA 
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Protocol version 6.0 from 26th September 2014 
calls. In addition, three patients were excluded because of additional treatment after completion of RFA 
(2 CPAP, 1 surgery). 
 
Discussing the limitations of their study, Friedman et al. (2007)59 attribute one of the study’ limitations 
to the large number of patients who are lost to follow-up, and declare “Unfortunately, many patients are 
not willing to return for a follow-up PSG”. Based on an "intent-to-treat" analysis the cure rate was 
37.2%. The authors estimate, however, that the "true" success rate is closer to 47.5% and state that, “it 
is possible that most of the patients who have had elimination of symptoms are those who are least 
likely to participate in the follow-up PSG”. In order to increase participation in the long-term follow-up 
visit,  patients  were  offered  free  adjunctive  treatment  such  as  additional  Pillar  implants  and  
radiofrequency tongue base reduction based on need as determined by the postoperative PSG. 
Apparently, most patients who were willing to participate in the follow-up visit, were those who had 
persistent snoring or symptoms and wanted additional treatment59.  
 
The problem of a high number of dropouts in long-term follow-ups is not limited to RFA studies. 
Walker et al. (2007)70, for example, conducted a study with an extended follow-up (15 months) that 
was based on an initial study with 90-days follow-up. Out of 53 patients that were enrolled to the initial 
study, 13 patients were either unable to be contacted or declined further participation; one site with 
seven patients from the initial study did not participate in the extended follow-up; seven patients did 
not meet the study inclusion criteria and four patients had other treatments for OSA (e.g., nasal CPAP, 
uvulopalatopharyngoplasty, laser-assisted uvulopalatoplasty) rendered during the extended follow-up 
period. Thus, the extended follow-up included only 22 patients (41.5%).  
 
Doff et al (2013)71, conducted a randomized study that compared outcomes of oral appliances(Group I) 
and CPAP (Group II) after 2 years follow-up. Out of 51 patients in Group I and 52 patients in Group II 
that started the clinical trial, only 29 and 37 patients (respectively) finished the 2-years follow-up study 
(64%). 
 
Considering these data the current study will have a follow-up period of 6 months after the last RFA 
treatment. The period of six months is chosen because 1) this is sufficient time for healing of the 
treated sites of the upper airways and, 2) it is enough time for following fortification or decline of 
therapeutic effects, 3) it is not so long that the strength of association of treatment and effect is lost, and 
4) it allows the possibility for longer term follow-up data on those patients who can be relied on for a 
longer follow-up. In addition, a six month follow-up time will allow for earlier identification of non-
responders so that these patients can be referred for additional therapy as indicated. 
 
 
3 
HYPOTHESES AND DATA ANALYSIS 
 
3.1 
Primary Efficacy Endpoints 
 
The primary effectiveness of the study is to demonstrate a clinically significant reduction of OSAS 
from Baseline PSG sleep study to the 6-month follow-up PSG in adults ( 22 years) with obstructive 
sleep apnea (AHI 10-30) and BMI  32.  
 

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Protocol 990211 RAMOSA 
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Effectiveness of the CelonProSleep plus will be assessed by demonstrating adequate reduction in AHI 
and ODI as defined below: 
 
 
A responder to the CelonProSleep plus RFA treatment is defined as a patient with an AHI 
reduction 50% and a reduction of their ODI 25% at the 6-month follow-up PSG, and their AHI at 
the 6-month follow-up is ޒ20.  
The aim of the study is to show that at least 50% of participants met the primary endpoint above. This 
will be tested with one sided 97.5% confidence interval with ±20% margin of error73, 74. 
 
In order to record and analyze data for determining the primary endpoints, patients will undergo a PSG 
sleep study to establish a mean baseline AHI and ODI. Patients will then be treated with a series of 
three treatments of upper airway radiofrequency ablation with the bipolar electrosurgical electrode 
CelonProSleep plus (Olympus Winter & Ibe, Germany) over 18 weeks. The patient will undergo a 
second PSG sleep study at the final follow-up examination 6-months later. Mean changes in AHI will 
be compared for each individual and among all patients. Surgical success is defined if at least 50% of 
participants experience at least 50% reduction in AHI and 25% reduction in ODI (Performance Goal, 
PG=50%). 
 
3.1.1 Experimental Design 
 
This is a single-arm assessment of AHI responder rate for treatment of obstructive sleep apnea 
compared to a performance goal (PG). Patients with 6-month post-treatment AHI measurements will be 
counted as a responder if they meet the performance goal. A subject will be counted as a non-responder 
(regardless of AHI measurement at 6 months) under the following circumstances: 
 
a. 
Death (any cause) between treatment and the 6-month follow-up 
b. 
Unsuccessful radiofrequency treatment attempt 
c. 
Need for an alternative OSA treatment before the 6-month follow-up 
d. 
Subjects who abandon the study 
e. 
Subjects who exit the study after the last treatment, but before the 6-month follow-up 
 
3.1.2 Subjects included in the Primary Efficacy Objective Analysis 
 
The primary efficacy analysis will include all subjects who received all three radiofrequency treatment 
procedures and the follow-up assessment at 6-months post-treatment.   
 
3.1.3 Hypotheses 
 
Null Hypothesis. Multi-level radiofrequency ablation of the upper airway in adults (age  22 years) 
with obstructive sleep apnea (AHI 10-30; Lowest O2 sat  80%) results in no improvement as defined 
by the composite endpoint, Section 3.1.  
 
H0:  TT RAMOSA  PG 
HA: TT RAMOSA ޓ PG, 

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where TTRAMOSA is the proportion of AHI and ODI responders to the multi-level radiofrequency 
treatment. For this objective, the PG is established at 50%.   
 
 
3.2 
Sample Size Rationale 
 
The sample size proposed for this study is 48 patients. This sample size is comparable to that used in 
performance and safety studies using radiofrequency ablation for the treatment of upper airways (soft 
palate and base of tongue, Table 1). In fact, considerable clinical data on the efficacy and safety RFA in 
OSAS is available from prior studies on this topic.  
 
Recommended sample size is n=48. Sample size is calculated for o the proportion of participants who 
meet the successes criteria as defined by the performance goal (PG) (Section 3.1).   
 
The following sample size considerations are based on the assumptions that PG=50% with 5% 
significance level and 80% power. 
The sample size of n=43 +10% dropouts, i.e. n=48, is calculated by using the normal approximation for 
the z-score for testing inference about a single proportion p; 
 
H0: P0 < 50%  
H1: P1  50% 
and P1-P0  20%   
 
Below is the output of PASS12 NCSS program for sample size calculation: 
 
Analysis of One Proportion Tests
Numeric Results for testing H0: P = P0 versus H1: P > P0 
Test Statistic: Z Test using S (P0) 
 
    Proportion 
 
 Given H0 Given H1 Difference 
Target 
Actual 
 Reject H0 
Power 
N 
(P0) 
(P1) 
(P1 - P0) 
Alpha 
Alpha 
Beta If Z  This 
 
Į=0.025                       
 
 
0.8029 
187 
0.5000 
0.6000 
0.1000 
0.0250 
0.0285 
0.1971 
1.9600 
0.8112 
82 
0.5000 
0.6500 
0.1500 
0.0250 
0.0299 
0.1888 
1.9600 
0.8081 
43 
0.5000 
0.7000 
0.2000 
0.0250 
0.0330 
0.1919 
1.9600 
0.81               26         0.5000         0.7500        0.2500         0.0250         0.0378         0.1805        1.9600 
 
Note that the one the actual exact Alpha of 0.033 will meet the two sided 5% significance. 
 
 
3.3 
Secondary Efficacy Endpoints 
 
To determine whether multi-level radiofrequency ablation of the upper airway in adults with OSAS 
with the CelonProSleep plus bipolar electrode improves daytime sleepiness, snoring, percentage sleep 

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time at SaO2 < 90%, and sleep-related quality of life without a significant increase in pain, speech or 
swallowing dysfunction. 
 
The following tools will be applied in order to determine the secondary aims: (1) Epworth Sleepiness 
Scale (ESS); (2) Functional Outcomes of Sleep Questionnaire (FOSQ), (3) SaO2, and (4) 100 mm VAS 
scale concerning snoring. ESS, FOSQ, and VASsnoring will be assessed at Baseline, 6 weeks after 
completion of each upper airway RF ablation treatments, and 6 months post-treatment. The percentage 
sleep time with SaO2 < 90% will be determined at the final 6-month PSG. 
  
Secondary endpoint statistical analysis includes descriptive statistics of percentages, Means and SD; In 
cases in which inference will be added to the value, it will be then corrected with Holm’s adjustment 
for testing multiplicity. 
 
3.3.1 Experimental Design 
 
Patients with 6-month post-treatment daytime sleepiness, snoring, and sleep-related quality of life 
measurements will be counted for statistical analyses as non-responders under the following 
circumstances: 
 
a. 
Death (any cause) between treatment and the 6-month follow-up 
b. 
Unsuccessful radiofrequency treatment attempt 
c. 
Need for an alternative OSA treatment before the 6-month follow-up 
d 
Subjects who abandon RAMOSA study 
e. 
Subjects who exit the study after the last treatment, but before the 6-month follow-up 
 
A specific description of analyses of the above secondary endpoints is given below. 
 
 
3.4 
Secondary Endpoints 
 
Secondary endpoints will be examined to provide additional support and details of the primary 
 endpoint findings concerning the RFA treatment. The secondary endpoints assess important patient-
based clinical outcomes to compliment the biophysiological primary outcomes. It will be evaluated 
using mean change at 6-months follow-up from baseline.  As supporting evidence, this will be tested 
with one-sided confidence interval with no corrections for multiple testing. 
 
 
3.4.1 Functional Outcomes Sleep Questionnaire (FOSQ) 
3.4.1.1 Description and Rational 
 
The FOSQ is a validated instrument that assesses the effect of a subject’s daytime sleepiness on 
activities of ordinary living. It is a quality of life measure that is commonly used in clinical evaluation 
and management of OSA. 

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3.4.1.2 Objective and Hypotheses 
 
The FOSQ secondary endpoint in this study will be determined by the FOSQ score at the 6-month 
follow-up compared with the pre-treatment Baseline. The objective is to demonstrate an improvement 
of daytime sleepiness measured by the FOSQ. 
H 0: 
PFOSQ  0 
HA: 
PFOSQ ޓ 0, 
where PFOSQ is the mean change of FOSQ from pre-treatment baseline to the 6-month post-treatment 
follow-up. This hypothesis will be tasted using one-sided 95% confidence interval around the mean 
FOSQ.   
3.4.2 Epworth Sleepiness Scale (ESS) 
3.4.2.1 Description and Rationale 
 
The ESS is a validated instrument that rates a subject’s daytime sleepiness. It is a quality of life 
measure that is commonly used in clinical evaluation and management of OSA. 
 
 
3.4.2.2 Objective and Hypotheses 
 
The ESS secondary endpoint in this study will be determined by the ESS score at the 6-month follow-
up compared with the pre-treatment Baseline. The objective is to demonstrate an improvement of 
daytime sleepiness measured by the ESS. 
H 0: 
PESS  0 
HA: 
PESS ޓ 0, 
where PESS is the mean change of ESS from pre-treatment Baseline to the 6-month post-treatment 
follow-up. This hypothesis will be tested using one-sided 95% confidence interval around the mean 
ESS.    
3.4.3   Visual Analog Scale (VASsnoring)  
3.4.3.1 Description and Rationale 
VAS is a validated instrument that rates different subjective parameters, including snoring. It is a 
quality of life measure that is commonly used in clinical evaluation and management of OSA. The 
VAS will be completed by the subject’s regular bed partner. 
3.4.3.2 Objective and Hypotheses 

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The VASsnoring secondary endpoint in this study will be determined by the VAS score at the 6-month 
follow-up compared with the pre-treatment Baseline. The objective is to demonstrate a reduction in 
snoring. 
H 0: 
PVAS  0 
HA: 
PVAS ޒ 0, 
where PVAS is the mean change of VAS from pre-treatment Baseline to the 6-month post-treatment 
follow-up. This hypothesis will be tested using one-sided 95% confidence interval around the mean 
VASsnoring.    
3.4.4 Percentage Sleep Time at SaO2 < 90% 
3.4.4.1 Description and Rationale 
 
The percentage of time spent with oxygen saturation below 90% has been an increasingly utilized 
surrogate for morbidity risk in certain sleep apnea populations.   
3.4.4.2 Objective and Hypotheses 
 
The SaO2 secondary endpoint in this study will be determined by the SaO2 percentage time below 90% 
during the 6-month PSG sleep study compared with the PSG sleep study at Baseline. The objective is 
to demonstrate a decrease in SaO2 percentage time at 6-months.   
H 0: 
PSaO2%time  0 
HA: 
PSaO2%time ޓ 0, 
where PSaO2%time is the mean change in Percentage time with SaO2 below 90% from Baseline to the 6-
month follow-up.  This hypothesis will be tested using one-sided 95% confidence interval around the 
mean SaO2.    
 
3.5 
Safety and tolerability of RFA Treatment 
 
Safety of radiofrequency treatment will be assessed via the description of all reported adverse events.  
Adverse events will be summarized by seriousness, severity, relatedness to the procedure and temporal 
relationship to the procedure. Acute adverse events are those within 14 days of each radiofrequency 
treatment, long-term adverse events are those events occurring from two weeks following the final 
treatment until the final 6-month follow-up. No formal statistical hypotheses will be tested. 
 
RFA specific adverse events and complications will be defined as follows (modified after Kezirian et 
al., 2005)45: 
- 
Minor: mucosal ulceration, mucosal crusting, or uvular sloughing,  

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- 
Moderate: hemorrhage that is controllable at the office, nerve paresis, or dysphagia to solid 
food, 
- 
Severe: palatal fistula, hemorrhage requiring hospitalization, nerve paralysis, dysphasia 
requiring tube feeding, and serious infection or airway compromise requiring hospitalization or 
surgical intervention. 
Tolerability of RFA treatment will be determined with various 100 mm VAS scales concerning pain, 
speech, and swallowing in order to capture patients’ perceived pain, and level of speech and 
swallowing functions after each RFA treatment. The VAS scales will be scored by the patient 
immediately following each RFA procedure and 1, 3 and 7 days post-procedure. The use and amount of 
narcotic pain medication (hydrocodone-acetominophen 5mg/325mg; Maximum 2 tablets every 6 hours, 
or 8 tablets per day; Narco®) by pill count will be recorded after each treatment. Mean score and the 
95% confidence interval for the tolerability VAS scales at each RFA visit will be calculated to capture 
tolerability profile. 
3.6 
Ancillary Data Collection 
In addition to the primary and secondary endpoint analyses, and to the analyses of RF procedure’s 
tolerability parameters, other supplementary data will be collected as part of the study protocol to 
ensure patient safety and for further examination of the effect of the therapy.   
These assessments will include summaries of all adverse events, information obtained during device 
interrogation (such as time of active RF treatment in each treated site of the soft palate and base of 
tongue, power in w, and amount of Joules), blood pressure measurements, and other sleep and 
cardiopulmonary parameters collected during the PSG sleep study. These assessments include, but are 
not limited to, the variables that follow: 
x Lowest Oxygen Saturation during Sleep (LSAT) 
x Mean Oxygen Saturation 
x Systolic and Diastolic blood pressure changes 
 
All data will be collected on case report forms at each site. Copies will be scanned and sent via 
email/fax to the sponsor’s data coordinators, who will enter the data and visually check for accuracy. 
The principal investigator at each treatment site will verify data accuracy. Data will be also checked 
statistically and inconsistencies will be resolved with the raw data at each site. 
 
 
4  
RESEARCH DESIGN   
 
The study is a prospective, single-arm, multicenter study designed to determine the effectiveness of 
multi-level radiofrequency ablation (RFA) for mild to moderate obstructive sleep apnea. The study 
aims to recruit a total of 48 patients at 3 study sites. The Medical University of South Carolina Hospital 
will serve as the primary site with 
the PI of the study. 
 
 
 

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4.1.1  Inclusion Criteria (Subjects) 
 
Patients who meet all of the following criteria may be given consideration for inclusion in this study: 
x Adults ( 22 years) 
x Self-report of daytime somnolence 
x Body mass index (BMI)  32 
x Mild to moderate obstructive sleep apnea (AHI 10-30; lowest O2 sat  80%)  OSA based on a 
prior PSG conducted within 12 months of enrollment, or based on a 2-night home sleep study 
using the WatchPAT 200S-3. 
x Evidence of palate and tongue base collapse on supine fiberoptic examination (Müller's 
maneuver ) 
x Have failed or have not tolerated CPAP treatment (See Section 5.1for definitions) 
x Have been offered and are not interested in oral appliance therapy 
x No prior surgical treatment for OSAS other than nasal surgery or tonsillectomy. 
x Willing and capable of providing informed consent  
x Willing and capable to return for all follow-up visits and PSG sleep-studies and filling out the 
questionnaires.  
 
4.1.2   Exclusion Criteria  
 
Patients who meet any one of the following criteria will be excluded from this study: 
x Another significant sleep disorder (e.g., insomnia, periodic limb movement) 
x Absence of regular bed-partner 
x Tonsillar hypertrophy (3 or 4 plus) 
x Chronic Obstructive Pulmonary Disease (COPD) 
x Interstitial Lung Disease (ILD) 
x Cystic Fibrosis 
x Acute Repiratory Distress Syndrome (ARDS) 
x Nasal or supraglottic obstruction on fiberoptic examination 
x ASA class III ,IV, V 
x Latex allergy 
x Lidocaine allergy 
x Pregnancy or plans to become pregnant 
      Note: women of childbearing potential must demonstrate a negative pregnancy test upon 
enrollment; those patients qualified to progress to RFA must also demonstrate a negative 
pregnancy test within 7 days prior to the date of RFA procedure. 
x Major depression or non-stabilized psychiatric disorder 
x Drug or alcohol abuse 
x Previous palatal or tongue surgery 
x Stable or unstable angina 
x CHF 
x moderate or severe valvular disease 
x TIA/CVA 

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x Carotid stenosis or endarterectomy 
x Anemia 
x Room air SpO2 < 95% 
x Pulmonary hypertension 
x Dialysis 
x Central or mixed apnea  10% of respiratory events 
x Participation in another clinical study (enrolled in any concurrent study) whose investigational 
plan is judged to interfere or affect any of the measures of this study 
 
4.2  
Sampling Methods 
 
A stratified sample is required to assure patient heterogeneity and representation of the mild and 
moderate patient in the sample. During recruitment, stratification according to the screening WatchPAT 
score will take place. Such stratification will be required within all participating medical centers. A list 
designating number of patients from each stratum will be distributed to the medical centers as part of 
study set-up. The screening WatchPAT score will serve to estimate AHI results and the patients’ 
stratum prior to recruitment. 
 
For the expected final sample size of n=48 the following stratification  
 
          Planed stratified sample scheme: 
Strata 
AHI level 
approximated by 
WatchPAT 
Required n
(%) 
Starta-1 
10-15
10 (21%) 
Starta-2 
15-20
12 (25%) 
Starta-3 
20-30
26 (54%) 
 
Participating sites are required to meet the specified strata distribution (percentages) as given for the 
entire sample. 
 
 
5  
PROCEDURES DURING THE STUDY 
 
5.1 
Visit 1 - Screening visit and home sleep study 
 
Patient medical records may be initially screened to determine whether an individual meets the general 
inclusion and exclusion criteria. In addition, the patient must have a history of CPAP failure or 
intolerance. For the purposes of this study, CPAP failure is identified as an inability to eliminate OSA 
(AHI remains greater than 10 despite CPAP usage). CPAP intolerance is identified by: 
• 
Inability to use CPAP (device indicates < 5 nights of per week of usage; usage defined as > 4 
hours of use per night76, as verified by 3-month CPAP smart card data, or 
• 
Unwillingness to use CPAP (e.g., patient returns the CPAP system after attempting to use it77). 

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The nature of CPAP intolerance will be specified in the medical records, reflect adequate attempts to 
pursue CPAP, and be documented by the study physician in the study database according to one or 
more of the following reasons. 
• 
Non-compliant and specific reasons for non-compliance including details of CPAP attempts 
• 
Experiencing discomfort because CPAP pressure is too high 
• 
Discomfort due to other reason (specify discomfort) 
• 
Causes undesirable clinical effects (specify undesirable clinical effect) 
• 
Patient not using the system enough (< 4 hours of use per night < 5 nights per week; the CPAP 
counter number will be documented) 
• 
Patient symptoms persist despite CPAP use 
 
If the patient meets this eligibility criterion, the patient will undergo a 2-night home sleep study using 
the WatchPAT 200S-3 to determine his/her screened AHI. The patient will be instructed in the use of 
the device and will return it to the office after the 2-night recording for interpretation. Patients who are 
qualified on the basis of the WatchPAT sleep study to participate in the study will be presented with the 
risks, benefits and alternatives to the study and will be asked to enroll in the study. 
 
Patients who meet all eligibility criteria and agree to participate in the study must provide written 
informed consent that has been approved by the center’s IRB. For patients who have a limited 
proficiency of the country’s language, the Sponsor will assist the center in obtaining a written 
translated consent. Translated consent forms must have IRB approval prior to use. 
 
If the patient does not qualify, the patient will be offered advice by the study physician for further 
management outside of the study. 
 
5.2 
Visit 2- Baseline visit and PSG sleep study  
 
This visit will occur within 2 weeks after the Screening Visit. During the Baseline visit, standard 
medical history and demographics will be obtained from each patient.  Patient descriptive information 
will include height and weight to calculate the body mass index (BMI), gender, blood pressure, heart 
rate, race, medications, use of alcohol, snoring history, effective CPAP pressure, and the information 
gained from the study’ questionnaires ((Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep 
Questionnaire (FOSQ)). 
 
In addition, the patient will undergo a Müller's Manoeuvre37, 38, a technique that looks for collapsed 
sections of the upper airways such as the oropharynx and hypopharynx. In this maneuver, a fiberoptic 
scope is passed into the upper airway through the nares while the patient is in supine position. The 
patient attempts to inhale with mouth closed and nostrils plugged. This leads to a collapse of the airway 
which can be directly observed with the fiberoptic scope.  Müller's maneuver is used to help determine 
the site of airway obstruction. A positive test result means observation of obstruction at either the 
retropalatal airway (soft palate; tonsils; lateral pharyngeal walls), retrolingual airway (base of tongue), 
or a combination of the two sites. Patients will be classified according to the method of Fugita75 as 
Class I if only retropalatal collapse is present; class II if both retropalatal and retrolingual collapse is 
present; and class III if only retrolingual collapse is observed.  

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Laboratory polysomnography (PSG) will be done no later than 90 days after enrollment and prior to 
first treatment. PSG will be conducted using standard techniques in the sleep laboratory. The AASM 
Manual  of  Scoring  Sleep,  2007  will  be  used  as  a  guideline  for  rules78, terminology and technical 
specifications for the PSG study in all study centers.  Briefly, the following list of recordings will be 
collected: 
 
1.   Three channels of electroencephalogram  
2.   Chin electromyogram 
3.   Two channels of electrooculogram  
4.   A single bipolar modified Lead II for electrocardiogram  
5.   Chest and abdomen belts for respiratory effort measurement  
6.   One oronasal thermal sensor to detect the absence of airflow for apnea  
7.   One nasal pressure transducer for detection of airflow for hypopnea  
8.   One finger oximeter to continuously monitor arterial oxygen saturation 
9.   One position sensor to electronically determine position (supine, left, right, prone), or a means 
      for documenting position 
10. One leg electromyogram to record leg movements 
 
All signals will be recorded on a digital PSG system and stored for off-line analysis by the PSG core 
lab.   
Prior to the PSG, the patients will fill out, or respond to, a Pre-PSG Interview that contains questions 
about recent behavior that may affect sleep during the PSG.   
 
During the PSG, the coordinator or PSG technician will fill out a PSG Log indicating technical aspects 
of the PSG recording that the Core Lab needs to score the PSG file, such as signal montage filtering 
and user events including body positions. The user events and body positions may be recorded directly 
onto the PSG recording system rather than on the PSG log if the recording system can create a readable 
file of the user notes that a core lab can use to assist with scoring.  
 
Subjects who fail to show mild-to-moderate OSA (AHI 10-30; Lowest O2 sat. > 80%) on the baseline 
PSG will not proceed to treatment and will be considered a screening failure. These subjects will be 
offered alternative therapy by their study doctor as indicated.  
 
 
5.3 
Visit 3- Stage I: First Radiofrequency Treatment (within 4 weeks of baseline PSG) 
 
The research team will greet the patient and will escort him to triage for vitals. The patient will then be 
escorted to the procedure room, and will be given oral antibiotics prior to the treatment. The patient 
will be asked to complete the specified questionnaires and VAS scales concerning, snoring (bed 
partner), speech and swallowing in order to capture patient’s baseline perceived pain and level of 
speech and swallowing function. VAS for pain will be conducted at the end of this session. The patient 
will be sitting upright in an examination chair. A crash cart is available in all units where the procedure 
is performed. Surgeons have both BLS and/or ACLS training. The patient will then undergo the first of 
three radiofrequency treatments to the upper airway. Radiofrequency ablation procedures will take 

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place in an outpatient setting under local anesthesia. The RFA procedure will be performed using 
standard surgical techniques and a new RFA applicator will be used for each of the 3 treatment visits. 
To perform RFA of the soft palate, a tongue blade will be inserted, bringing the palate into view. The 
soft palate will be anesthetized with three sprays  of  topical anesthetic using a typical spray applicator 
(benzocaine 14%, butamben 2.0%, tetracaine hydrochloride 2.0%; Cetacaine®) followed by an 
injection of 8 to 10 cc of 1% lidocaine with 1:100,000 epinephrine. The physician will then insert the 
surgical handpiece needle electrode into the submucosal tissue of the soft palate. The radiofrequency 
generator delivers energy beneath the surface tissue while monitoring temperature. Tissue is heated in a 
limited area around the needle electrode, creating a coagulative lesion beneath the surface. The energy 
application is immediately aborted if there are signs of tissue blanching on the mucosal surface. 
Discomfort is minimal during the procedure and the surface tissue is protected from thermal damage by 
the submucosal lidocaine infiltrate which expands the thickness of the soft palate tissue. A single-prong 
RFA applicator (CelonProSleep plus, Olympus, Germany) is used to create 7 lesions of 54 joules (J) 
each (Celon Power Setting 12W, as indicated in the Instruction for Use): two laterally above the 
anterior tonsillar pillar; two paramedian to the uvula; and three at the hard and soft palate junction (Fig. 
1).  
 
 Following the procedure, the patient rinses his/her mouth with cool tap water. The throat is checked in 
5 minutes by the surgeon to make sure there is no ongoing oozing. In the event of ongoing ooze, the 
spot will be treated with a stick of silver nitrate cautery.  
 
 
 
 
 
   Fig. 1 Points of RF treatment – soft palate 
 
The 7 lesions in the documented positions provide sufficient energy application to the soft palate 
without concern of extensive energy overlap. A 54 J lesion creates an average lesion size of 0.40 cubic 
centimeters, and each lesion is a centimeter or more removed from the adjacent lesion. The probe is 
placed in the submucosal tissues so that the probe cannot be seen through the overlying mucosa. The 
physician will perform a gentle tug on the probe once inserted to make sure that it is in the proper 
position within the palatal muscles and not within the submucosal tissues. The natural contour of the 
probe prevents penetration through the soft palate, and the generator will fail to activate if the tip of the 
probe is not within tissue. 
 

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To perform RFA of the tongue base, the anterior tongue is grasped by the surgeon with clean gauze. 
The tongue is sprayed with 3 sprays of topical anesthetic (benzocaine 14%, butamben 2.0%, tetracaine 
hydrochloride 2.0%; Cetacaine®) followed by an injection of 6 cc of 1% lidocaine with 1:100,000 
epinephrine in the middle third of the tongue posterior to the circumvallate papillae. The patient then 
undergoes 6 lesions of RFA each placed 1cm from the midline for a total of three lesions on either side 
of the tongue. The tongue base is the posterior 1/3 of tongue posterior to the anterior tonsillar pillars 
and circumvallate papilla. The area to be treated corresponds to the middle third of the tongue base 
which includes the highest dorsum of the tongue and 1 centimeter to either side of the midline (Fig. 2). 
The CelonProSleep plus single prong applicator will then be used to create the 6 lesions spaced 
approximately 1 cm apart of 80-84 J each (Celon Power Setting 7W, as indicated in the Instruction for 
Use). As higher power settings lead to smaller lesion sizes, the recommended power settings for soft 
palate and base of tongue were chosen to fit into the body structure without endangering the mucosa if 
the lesion becomes too big.  
 
After the RF treatment, the patient then rinses his/her mouth with cool tap water. The throat is checked 
in 5 minutes by the surgeon to make sure there is no ongoing oozing. In the event of ongoing ooze, the 
spot will be treated with a stick of silver nitrate cautery. 
 
 
 
 
 
     Fig 2 Points of RF treatment – Base of tongue 
 
After completion of both RFA procedures, the research team will monitor the patient for up to 3 hours 
post-procedure. Patients must demonstrate adequate pain control, breathing, swallowing and speech 
prior to discharge. The patient’s vitals will be taken prior to the patient being released from the 
clinic. The research team will ask the patient to walk around the clinic for five minutes to assess the 
patient’s post-operative status. The patient will be provided prescriptions for an antibiotic (amoxicillin 
or clindamycin), an oral steroid (7-day methylprednisolone taper pack), and an oral pain medication to 
take if needed (Acetaminophen/Hydrocodone). In addition, the patients will be asked to have a soft diet 
for at least 2 days after the RFA treatment. The patient will then repeat the questionnaires specified 
above. Patients will be asked in advance to have their bed partner present to drive them home. The 
research team will escort the patient and bed partner out to the car. Each patient will be provided an 
emergency contact number to allow them to contact study personnel or their designees 24-hours a day. 
The patients will repeat the pain, speech, and swallowing VAS scales at 1, 3, and 7 days post RFA 
treatment via telephone in order to document persistent ongoing pain, and post-treatment discomfort. 
The number of pills of narcotic pain medication (hydrocodone-acetominophen 5mg/325mg; Maximum 
2 tablets every 6 hours, or 8 tablets per day; Narco®) used in the first 7 days following the procedure 
will be recorded.  

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Clinical examination and assessment of the palate and base of tongue will be performed at days three 
and 10 following each RF procedure to observe effects on speech and swallowing, as well as other 
complications as described in the Table below.  
 
Following medical actions will be taken in case of development of side effects and/or complications 
due to the RFA treatment: Minor and moderate complications such as mucosal ulceration, mucosal 
crusting, uvular sloughing, hemorrhage controllable in clinic, palatal edema, mild dysphagia,  and local 
infection can be managed with antibiotics, topical medicated gargles, and regular follow-up until the 
events resolved. Severe complications such as tongue abscess or airway distress due to edema may 
require hospitalization for medical care (IV fluids; steroid; antibiotics) and/or surgical intervention 
(airway support; abscess drainage). In a case of an emergency situation arise in the office each 
treatment center should be fully equipped with crash cart and should have access to a full array of 
endoscopic and surgical instruments. Rapid transport to an Emergency Department should be available 
should the need arise.  
 
 
5.4 
Visit 4 – Stage II: Second Radiofrequency Treatment (6 weeks later) 
 
The study physician will perform a brief history and examination to make sure the patient tolerated the 
first treatment well and that the patient’s tissues are fully healed with no visible ulceration or 
granulation. If there is a complication such as abscess and ulceration, the second treatment will be 
delayed until patient’s tissues are fully healed. The patient will be given oral antibiotics and will then 
undergo a second treatment as outlined above. Treatment will be done in the same region and location 
since there is no concern about RFA lesion overlap once the tissues have healed. The patient will be 
prescribed pain medication if needed, along with a short course of oral antibiotics and steroids as 
outlined above.  
 
After completion of both RFA procedures, the research team will monitor the patient for up to 3 hours 
post-procedure. Patients must demonstrate adequate pain control, breathing, swallowing and speech 
prior to discharge. The patient’s vitals will be taken prior to the patient being released from the 
clinic. The research team will ask the patient to walk around the clinic for five minutes to assess the 
patient’s post-operative status. The patient will be provided prescriptions for an antibiotic (amoxicillin 
or clindamycin), an oral steroid (7-day methylprednisolone taper pack), and an oral pain medication to 
take if needed (Acetaminophen/Hydrocodone). In addition, the patients will be asked to have a soft diet 
for at least 2 days after the treatment. The patient will then repeat the questionnaires specified above. 
Patients will be asked in advance to have their bed partner to drive them home. The research team will 
escort the patient and the bed partner out to the car as outlined above.  
 
The patients will repeat the pain, speech, and swallowing VAS scales at 1, 3, and 7 days post RFA 
treatment via telephone in order to document persistent ongoing pain, and post-treatment discomfort. 
The amount of narcotic pain medication used in the first 7 days following the procedure will be 
recorded using pill count. 
 

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Medical examinations and medical actions needed due to development of side effects and/or 
complications will be the same as described in Section 5.3 above. 
5.5 
Visit 5 - Stage III: Third Radiofrequency Treatment (6 weeks later) 
 
The doctor will perform a brief history and examination to make sure the patient tolerated the second 
treatment well and that the patient’s tissues are fully healed. If there is a complication such as abscess 
and ulceration, the third treatment will be delayed until patient’s tissues are fully healed.  The patient 
will be given oral antibiotics and will then undergo a third treatment as outlined above. Treatment will be 
done in the same region and location. The patient will be prescribed pain medication if needed, along 
with a short course of oral antibiotics and steroids as outlined above. 
 
After completion of both RFA procedures, the research team will monitor the patient for up to 3 hours 
post-procedure. Patients must demonstrate adequate pain control, breathing, swallowing and speech 
prior to discharge. The patient’s vitals will be taken prior to the patient being released from the 
clinic. The research team will ask the patient to walk around the clinic for five minutes to assess the 
patient’s post-operative status. The patient will be provided prescriptions for an antibiotic (amoxicillin 
or clindamycin), an oral steroid (7-day methylprednisolone taper pack), and an oral pain medication to 
take if needed (Acetaminophen/Hydrocodone). In addition, the patients will be asked to have a soft diet 
for at least 2 days after the treatment. The patient will then repeat the questionnaires specified above. 
Patients will be asked in advance to have their bed partner drive them home. The research team will 
escort the patient and bed partner out to the car as outlined above.  
 
The patients will repeat the pain, speech, and swallowing VAS scales at 1, 3, and 7 days post RFA 
treatment via telephone in order to document persistent ongoing pain, and post-treatment discomfort. 
The amount of narcotic pain medication used in the first 7 days following the procedure will be 
recorded. 
 
Medical examinations and medical actions needed due to development of side effects and/or 
complications will be the same as described in Section 5.3 above. 
 
5.6 
Visit 6 - Follow-Up Visit (6 weeks later) 
 
The patient will undergo complete post-treatment evaluations including sleep history and physical 
examination (including height, weight, and blood pressure) as done in Baseline Visit. The patient will 
be asked to complete questionnaires including Epworth Sleepiness Scale (ESS), Functional Outcomes 
of Sleep Questionnaire (FOSQ) and 10 cm VAS concerning pain, snoring (bed partner), speech, and 
swallowing. The study physician will inform the patient on his/her study results and medical condition 
and will give recommendations for ongoing management as needed. 
 
5.7 
Visit 7- Final Follow-up Visit (6-Months later after last RF treatment) 
 
The patient will undergo complete post-treatment evaluations including sleep history and physical 
examination (including height, weight, and blood pressure) as done in Baseline Visit. The patient will 
be asked to complete questionnaires including Epworth Sleepiness Scale (ESS), Functional Outcomes 
of Sleep Questionnaire (FOSQ) and 10 cm VAS concerning pain, snoring (bed partner), speech, and 

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swallowing. In addition, each patient will undergo a second PSG sleep study not later than 30 days 
after the Final Study Visit. The PSG sleep study will be conducted using standard techniques in the 
sleep laboratory as defined in section 5.2 above. 
 
5.8 
Visit 8 – Final Study Visit (after the PSG sleep study) 
 
Shortly after the 2nd PSG study, the study physician will inform the patient on his/her study results and 
medical condition and will give recommendations for ongoing management as needed. 
 
 
6 
DURATION 
 
This study has a minimum of eight visits. The first visit, the Screening Visit, is planned for determining 
whether patient qualifies for the study. This visit will take up to 1 hour. In the second visit, the Baseline 
Visit, which occurs up to 2 weeks later, standard medical history, demographics and various 
questionnaires will be obtained from the patient. In addition, the patient will undergo a Müller's 
Maneuver and will be sent to the sleep lab for a PSG study (one night). This visit will last about 60 
minutes. 
The third visit is the first RF treatment session and will last about 1 hour. The fourth and fifth visits 
involve additional RF treatments and will last about one hour each. The first follow-up visit will occur 
6 weeks after the third treatment visit and will last as well about 1 hour. The 7th visit, the 6-month 
follow-up visit, will occur 6 months later and will be no more than 1 hour. At the end of this visit the 
patient will be admitted to a sleep labor for undergoing the 2nd PSG study. Finally, the 8th and final 
Visit will last about 30 minutes. The patients may require additional visits in case of complications that 
are needed to be treated in the hospital or if they have a question or concern. The entire duration of the 
study for an individual patient is no longer than 24 weeks plus 6 months of follow-up. 
 
7  
INSTRUMENTS   
The following outcome measures will be utilized to represent meaningful measurements of therapy 
success:   
1. Apnea-hypopnea index (AHI) - is an index of sleep apnea severity that combines the frequency of 
apnea and hypopnea events. The severity of obstructive sleep apnea is determined by the measurement 
of apneas and hypopneas.  An obstructive apnea is defined as a cessation (> 90% decrease) of airflow 
for at least 10 seconds with breathing effort; and a hypopnea is defined as an event with at least a 30% 
reduction in airflow lasting at least 10 seconds, and with  4% oxygen desaturation.  The frequency of 
apneas and hypopneas per hour of sleep is termed the apnea-hypopnea index (AHI). AHI values are 
typically categorized as 5–15/hr = mild; 15–30/hr = moderate; and > 30/h = severe. AHI will be 
determined at baseline and at the 6-months follow-up visit.  
2.  Oxygen Desaturation Index (ODI) – ODI is defined as the number oxygen desaturation events, 
where there is a  4% desaturation from pre-event baseline, that occur per hour of sleep.  ODI generally 
correlates well with AHI [15], and it is reasonable to conclude that a 25% reduction in ODI represents a 

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clinically meaningful improvement.  ODI will be determined at baseline and at the 6 months follow-up 
visit. 
3.    Epworth  Sleepiness  Scale  (ESS)  -  The  ESS  is  a  validated,  self-report  instrument  that  rates  a  
subject’s tendency to fall asleep in eight common daily situations.  The ESS Scale has been validated 
primarily in OSA.  It is used to measure excessive daytime sleepiness, and is often utilized before and 
after the administration of treatment (e.g. CPAP) to document improvement of symptoms.  The patient 
will complete this questionnaire at the Baseline, at Visit 3 (prior to the 1st RFA treatment), Visit 4 
(prior to the 2nd RFA treatment), at Visit 5 (prior to the 3rd RFA treatment), at Visit 6 (6 weeks follow-
up post 3rd RFA treatment), and at Visit 7 (6 months follow-up). 
4.  Functional Outcomes of Sleep Questionnaire (FOSQ) - The FOSQ is a quality-of-life questionnaire 
designed specifically to evaluate the impact of disorders of excessive sleepiness on activities of daily 
living. This is a self-report measure that assesses the effect of excessive sleepiness on activities of 
ordinary living, including activity level, vigilance, intimacy and sexual relationships, general 
productivity, and social outcomes. The patient will complete a FOSQ at the Baseline, at Visit 3 (prior 
to the 1st RFA treatment), Visit 4 (prior to the 2nd RFA treatment), at Visit 5 (prior to the 3rd RFA 
treatment), at Visit 6 (6-Weeks follow-up post 3rd RFA treatment), and at Visit 7 (6-months follow-up). 
5. Pain will be measured on a 10-point Visual analog Scale (VASPAIN, 0 = “no pain” and 10 = “severe 
pain”). Measurements will be done on day 1, 3, and 7 post (each) RFA treatment.  
 
6. Snoring will be measured on a 10-point Visual analog Scale (VASSNORING) and filled out by the bed 
partner. This scale will be used to asses by the patient and his/her bed partner snoring levels. The scale 
will range from 0 (no snoring noise) to 10 (extreme noise - bed partner leaves the room). Measurements 
will be done on day 1, 3, and 7 after the first RFA treatment, on the 2nd and 3rd RF treatments, prior to 
the treatment and on both follow-up visits. 
 
7. Functional parameters such as speech and swallowing will be measured on a 10-point Visual analog 
Scale (VASSPEECH /  VASSWALLOWING) ranging from zero (no problems/not affected) to 10 (severe 
problems/severely affected). Measurements will be done on day 1, 3, and 7 post each RFA treatment. 
 
 
8  
STATISTICAL ANALYSES 
All analyses and graphs will be performed with common statistical packages. In general, summary 
statistics will consist of the following:  
Continuous variables will be summarized by the number of observations (n), the mean, the standard 
deviation (SD), the standard error (SE), the median, the minimum, maximum and 95% confidence 
limits about the mean. 
Categorical variables will be summarized by frequency and percentage in the corresponding categories 
and associated 95% confidence limits.   

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8.1 
Primary Efficacy Endpoint 
 
The primary endpoint of AHI and ODI obtained at the 6-month follow-up will be compared to the 
Baseline measurement. The subject is a responder if the reduction in AHI is  50%, and ODI reduction 
is  25%. The proportion of subjects meeting the responder criteria among all included subjects will be 
evaluated using a one-sided 95% confidence interval. In addition one sample test of the proportion of 
patients meeting the PG at 6month is significantly different than 50%. The study is designed to 
demonstrate success rate of 20% beyond the PG of 50%.  Proportion with 95% CI will be given using 
normal approximation to the Binomial. P-Value will be derived based on the exact binomial 
distribution of the null hypothesis, that is assuming p=0.5. 
8.2 
Additional Analysis 
 
Demographic, medical history and operative characteristics will be summarized for the study cohort, by 
clinical site, and by groupings of all sites. At a minimum, this will include age, gender, race, weight, 
and BMI.  
 
Supporting analyses will be conducted to provide additional information on the safety and efficacy of 
multi-level radiofrequency treatment. Descriptive statistics will be utilized to summarize all adverse 
events. Regression models evaluating the change of continuous outcomes of AHI and ODI as well as 
logistic regression for the categorical outcome of response to treatment as defined in the primary 
objective will be used. A description of the relationship between BMI change and effectiveness 
outcomes will be performed by a cross-tabulation of BMI change versus responder and non-responder 
groups.   
 
Data collected on all enrolled study subjects will be analyzed on an intend-to-treat and as-treated basis.  
Disease information and demographic variables, such as age, ethnic group, and sex, will be 
summarized by means of summary statistics. A normality distribution test (Kolmogorov-Smirnov) will 
be performed for all variables. Simple descriptive statistics such as frequency, mean, standard 
deviation, minimum, and maximum will be calculated for all outcome variables. If these variables are 
not normally distributed, other descriptive measurements such as median and the interquartile range 
will be calculated.  For comparison between pre- and post-treatment variables, McNemar’s will be used 
with categorical variables. For continuous variables, a paired t-Test (normal distribution) or a Wilcoxon 
signed rank Test (not normal distribution) will be used to compare data at visit 2 (Baseline) and at visit 
6 (six weeks after final RFA treatment). In addition, for long longitudinal analysis a One-Way ANOVA 
with Repeated Measures (or mixed models) will be used to model the outcome and cofactors over the 
multiple time-points. Significant interactions will be followed up using post-hoc analysis with Holms’ 
adjusted P-values. 
 
Site homogeneity will be evaluating by testing the interaction term in the analysis of covariance 
(ANCOVA) at a significance level of 0.15. 
 
8.3 
Statistical Power Considerations 
 
According to the sample size calculation (section 3.2) the actual expected power is 80.8%. 

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8.4 
Analysis Sets 
The following defines the analytic sample for the relevant endpoint used in a particular analysis. 
Safety Analysis Set (SAS): The safety analysis set will include all subjects who receive radiofrequency 
treatment. 
Full Analysis Set (FAS): The full analysis set will include all subjects who receive radiofrequency 
treatment and completed all 8 visits of the study.   
8.5 
Handling of Missing Data, Subject Withdrawals, and Treatment Failures 
Subjects that are lost-to-follow-up will be categorized as treatment failures from the time point of 
dropout forward. Sensitivity analyses will also be conducted excluding lost-to-follow-up subjects to see 
what impact, if any, they might have on the overall results of clinical activity. Time-to-event analyses 
will consider these subjects as censored at the lost-to-follow-up time point. All data will be recorded on 
a CRF forms and will be subjected to regular monitoring. 
Every effort will be made to follow subjects for study observation and encourage compliance with 
study measurements to minimize the amount of missing data. 
8.6 
Interim Analyses 
There are formal interim analyses planned for the first 15 patients and then every 15 completed 
patients. Review of safety data will be evaluated on a continual basis throughout the study. Review of 
safety data by a Clinical Research Office (CRO) for the purpose of general safety review will be done; 
however, the review of such data is not intended to impact the study conduct unless there are safety 
concerns. As such, it is expected that the trial will continue to its scheduled completion barring any 
unexpected safety issues. 
 
 
9  
RISK ANALYSIS 
 
9.1 
Risks of Confidentiality 
 
(1) Each patient at the time of enrollment will be assigned a subject number. The codebook linking the 
patient identifiers to the subject number will be keep in a locked cabinet in the locked office of each 
Principal Investigator. The subject number is the number that will appear on all study related 
documents. 
 
(2) Study staff will be trained on the importance of confidentiality.  All medical information recorded 
as part of the study will be captured using pre-printed standardized forms (Case Report Forms) specific 
to the study. The only identifier on the forms will be the subject study number. The forms for a given 
subject will be kept in individual study folders and stored in a locked cabinet in the locked office of the 
study coordinator.   

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(3) All adverse events and serious adverse events will be documented in the subject study folder.  
Serious adverse events will be immediately communicated to the institutional IRB per standard 
protocol. 
 
9.2 
Risks and Discomforts  
 
The direct risks of radiofrequency ablation of upper airway tissues include the following: 
(1) Risk of bleeding - The use of a probe inserted into upper airway tissues will result in minor 
bleeding. The amount of bleeding is minimal due to the use of epinephrine and the superficial nature of 
the procedure. Bleeding, if present, can be controlled with pressure, silver nitrate cautery, and/or suture 
ligature. All surgeons will have many years of experience with radiofrequency ablation.  
 
(2) Risk of pain or discomfort - Needle and probe insertion into the tissue will cause mild pain and 
discomfort that is typically well tolerated in an awake patient. The patient will be given topical 
anesthetic and a local anesthetic of lidocaine prior to the procedure, and is therefore expected to have 
minimal discomfort.  
 
(3) Risk of hematoma - The use of a needle and probe will result in some bleeding and the possibility 
of hematoma (swelling of blood or clot) formation. The risk of this uncommon complication is 
expected to be minimal, and the use of epinephrine in the lidocaine additionally reduces the risk of 
hematoma formation. Observed hematomas will be drained under local anesthesia in order to prevent 
breathing or swallowing issues. 
 
 (4) Risk of infection or abscess - The procedure involves penetrating tissue with the probe which has 
the potential risk of infection. This risk is minimized by the use of antibiotics and steroids after each 
treatment. Patients will be followed closely after the procedure to assess for signs and symptoms of 
infection and/or abscess.       
 
(5) Nerve Trauma - This is a theoretical risk since the application of the RFA energy will be applied far  
from the natural landmarks of the lingual and hypoglossal nerves. 
 
(6) Dysphagia - Slight difficulty in swallowing is common but all patients are expected to resume at 
least a diet of soft foods immediately following the procedure. It is anticipated that all patients will 
resume a normal diet by post-procedure day 3. 
 
(7) Procedure Duration- This is a theoretical risk.  However, the CelonProSleep plus has a built-in 
automatic turn-off system shuts off after delivering certain amount of energy.   
 
(8) Other risks may include airway problems, nasopharyngeal stenosis, ulceration of the treated site, 
paresthesias, edema of tongue, change in speech, and other possible unexpected symptoms. 
 
9.3 
Minimization of Risk to the Patient 
 
Risks can be minimized through the use of proper surgical procedures, compliance with this protocol 
and device specifications, adherence to the guidelines for patient selection, close monitoring of the 

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subjects’ physiologic status during treatment and follow-up procedures, and by promptly supplying the 
Sponsor with all pertinent information required by this protocol.   
 
The surgical risks are minimized in this study by including OSA subjects who do not have significant 
co-morbidities, utilizing surgeons who have previous clinical experience and thorough protocol related 
training prior to initiation of the clinical trial.  RAMOSA study surgeons must be familiar with neck 
surgery, the tongue and pharyngeal muscle movements, and have previously used RFA in the treatment 
of snoring.   
 
Additional measures will be taken to minimize risk to subjects as part of this investigational plan: 
• Reported adverse events will be reviewed regularly and reported to the sponsor throughout the study.   
Any severe adverse event will be reported to the institutional IRB and sponsor in a timely fashion.  
Appropriate medical measures will be immediately taken to resolve all adverse events. 
 
9.4 
Potential Benefits 
 
Although no assurances or guarantees can be made, there is a reasonable expectation that the use of 
radiofrequency ablation may be beneficial. Radiofrequency ablation (RFA) of the upper airway using 
FDA-cleared devices has demonstrated promise as a treatment alternative for obstructive sleep apnea in 
multiple published studies 29-31, 34. In these studies, repeated RFA of the soft palate and base of tongue 
region resulted in significant reductions in AHI and daytime sleepiness without significant 
complications. RFA has several advantages over traditional surgical approaches including its ability to 
address multiple levels of the airway (nose, palate, tongue); ability to perform in the office under local 
anesthesia; lower cost; and minimal pain and morbidity. The CelonProSleep plus, the study device used 
in this study, is similar to other FDA-cleared RFA devices (e.g. Gyros or Somnos) but delivers the RF 
energy more rapidly thereby adding to patient comfort during the procedure. In addition, due to the 
bipolar electrode the CelonProSleep plus device coagulates much faster (although the power setting is 
less) than the Gyrus or Somnos systems. Therefore, less energy is needed to reach the coagulation 
threshold of the tissue. 
 
 
10 
ADVERSE EVENT MANAGEMENT 
 
Timely, accurate, and complete reporting and analysis of safety information for clinical studies is 
crucial for the protection of subjects, Investigators, and Sponsor. Data collected in this study may be 
used in support of global regulatory approvals.  Sponsor has established procedures in conformity with 
worldwide regulatory requirements to ensure appropriate reporting of safety information.  This study is 
conducted in accordance with these procedures and regulations. All adverse events and adverse device 
effects will be reported to all Institutional Review Boards (IRB’s). At each evaluation, the investigator 
will determine whether any adverse events (AEs) have occurred. Detailed information regarding such 
adverse events will be recorded on a specific case report form (CRF) for adverse events. Investigators 
will be asked to make a judgment as to the relationship of the event to the study device. Follow-up data 
to ascertain the existence of residual effects from the event will be obtained. 
 
 

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10.1 
Definitions 
 
For the purpose of this protocol, the following definitions shall apply: 
 
10.1.1 Adverse Event (AE) 
 
An adverse event (AE) is any untoward medical occurrence in a subject (without taking into account 
the relationship with the device under investigation). The AE can be any unfavorable or unintended 
sign, symptom, or disease temporally associated with the use of the device (ICH E2A). All new and/or 
worsening adverse events (AE) will be collected throughout the study duration, starting when the 
subject is enrolled into the study (when the Subject Informed Consent is signed) and reported to the 
Sponsor on an Adverse Event Case Report Form. In addition, all deaths must be reported. Documented 
pre-existing conditions are not considered adverse events unless there is a change in the nature or 
severity of the condition and required additional medical or pharmacological treatment.   
All adverse events should be followed until the adverse event has been resolved, is ongoing with no 
further actions to be taken, the subject exits the study or until study closure, whichever occurs first. 
Investigators will categorize AE’s according to their severity and relatedness (e.g., to the surgical 
procedure, to the CelonProSleep plus, etc.). The Sponsor will then review all reported adverse events 
for completeness, and ask for clarification or additional information if necessary.    
 
AE Definitions for Investigator Classification 
Investigators are responsible to categorize adverse events according to their seriousness and 
relatedness. The definitions for classifications are included below. Those events that do not meet the 
criteria for Serious Adverse Event are considered non-serious.   
 
10.1.2 Adverse Device Effect (ADE) 
Any untoward and unintended response to a medical device. This definition includes any event 
resulting from insufficiencies or inadequacies in the instructions for use or the deployment of the 
device. This definition includes any event that is a result of a user error: 
10.1.3 Serious Adverse Event (SAE) 
 
A serious adverse event is an adverse event that: 
(1) Led to death 
(2) Led to a serious deterioration in the health of the subject that: 
-Resulted in life-threatening illness or injury (the patient was at substantial risk of dying at the 
time of the adverse event or it is suspected that the use or continued use of the product would 
result in the patient’s death); 
-Resulted in permanent  impairment of a body function or permanent damage to body structure; 
or necessitates medical or surgical intervention to preclude permanent impairment of a body 
function or permanent damage to a body structure; 
 
-Required in-patient hospitalization or prolongation of existing hospitalization;    
 
-Resulted in medical or surgical intervention to prevent permanent impairment to body structure 
or a body function.  
 
 

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10.1.4 Serious Adverse Device Effect (SADE) 
 
A Serious Adverse Device Effect is and Adverse Device Effect that has resulted in any of the 
consequences characteristic of a SAE or that might have led to any of these consequences if suitable 
action had not been taken or intervention had not been made or if circumstances had been less 
opportune. 
 
10.1.5 Relatedness 
 
Investigators are also responsible to categorize adverse events according to their relatedness.  The 
definitions for relatedness classifications are included below.    
 
10.1.5.1 
Surgical Procedure Related 
 
Surgical procedure related adverse events are those that are related or possibly related to the procedures 
involved in the CelonProSleep plus or those normally associated with a surgical procedure.  These 
events typically occur within 10 days of treatment.     
 
10.1.5.2 
Other Surgical Procedure Related 
 
Other surgical procedure related adverse events are those that are normally associated with a surgical 
procedure, but the surgical procedure was not associated with the CelonProSleep plus.       
10.1.5.3 
Pre-existing or Independent Condition Related  
 
Any event, although temporally associated, that was attributable to a preexisting or independent 
condition.  .   
 
10.1.5.4 
Other 
 
Any event that cannot be classified in any of the above categories. 
 
10.2 
AE Definitions for Sponsor Classification 
 
10.2.1 Unanticipated Adverse Device Effect (UADE)  
 
Any serious adverse effect on health or safety or any life threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the CIP or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects..   
 
10.2.2 System component-relatedness 
 
Adverse events that are System-related will be further assessed by the Sponsor according to whether 
the event resulted from the presence or performance of the surgeon.   

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10.3 
Adverse Event Adjudication  
 
Upon receipt, adverse event CRFs are reviewed for completeness by the Sponsor and Sponsor will 
request clarification and/or additional information from the Investigator, when necessary. The Sponsor, 
with the assistance of the Investigator, will also determine whether an event is reportable to regulatory 
agencies / competent authorities. A Clinical Events Committee (consisting of independent physicians) 
will review serious adverse events at regular intervals. The CEC is responsible for reviewing the 
Investigator’s assessment and classification of each event.   
 
10.4 
Adverse Event Outcome Status  
 
Adverse Events when reported are assigned an “open” or “closed” outcome status by centers depending 
on the nature of the event or the corrective action involved. When clinically appropriate, centers should 
work to close events that may not be resolvable during the term of the investigation. Centers may move 
outcome status to “closed” or alternatively, add text to the adverse event description at follow-up visit 
addressing that the adverse event is ongoing but for study purposes and outcome data, the event is 
considered closed. 
An  Event  is  “closed”  if  the  subject/event  is  fully  recovered  or  partially  recovered  and  no  further  
recovery is expected.   
An Event is “open” if the subject/event is partially resolved, unchanged, or worsened, or further 
recovery is otherwise expected.  In the case the Event remains open, continue to follow this Event on 
an adverse event form at each follow-up visit until the event is closed. 
 
10.5 
Notification of Serious Adverse Events 
 
The Investigator will report any SAE to the Sponsor as soon as possible, but not later than 24 hours 
after the investigator learns of the event. All SAEs should be documented on the Adverse Event Case 
Report Form and an explanation of any medical treatment administered or surgical intervention should 
be provided. The form must be completed, signed and sent by fax to the Sponsor within 24-hours of 
learning of the adverse event. 
 
The SAE report must be followed by a full written report 
 
10.6 
Subject Deaths  
 
A subject death during the study must be reported to Sponsor as soon as possible.  IRB regulations 
and/or Ethics Committee requirements may require notification of the study Sponsor within 24 hours of 
learning about the event. The center’s IRB/MEC must be notified of any deaths in accordance with that 
center’s IRB/MEC policies and procedures. 
Notification of death must include a detailed narrative (death letter) that provides detailed information 
describing the circumstances surrounding the death and is signed by the principal Investigator or 
authorized co-Investigator.  The death letter must include all of the following:  
 
a) 
Date and time of death 
b) 
Place death occurred 

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c) 
Immediate cause of death 
d) 
The relatedness of the death to the CelonProSleep plus, surgical procedure, clinical  
investigation, or subject condition. 
e) 
Whether or not the death was witnessed 
f) 
Device status and/or activity at the time of death  
g) 
Any other circumstances surrounding the death 
h) 
Approximate time interval from the initiating event to death (temporal course) 
i) 
Investigator or co-Investigator signature and date 
j) 
Any information listed above that is unavailable or unknown must be specified in the death 
letter. Also submit the following documentation: 
 
If the subject expired in the hospital, A copy of the medical records for that admission (e.g.  
H & P, consults, test results, operative reports, and/or progress notes from the hospital chart) 
 
Death certificate (if available) 
 
Autopsy report (if applicable) 
 
A copy of the most recent clinic visit (if not already submitted to Sponsor) 
 
Death certificate (if available) 
 
Obituary (if able to obtain) 
 
Data collected from the subject up to the point of death will remain documented on CRFs and/or 
worksheets.  In addition to the Patient Status Change CRF, these may include the adverse event forms 
(if applicable), and Device Status Change CRF.    
 
 
CelonProSleep plus and related Sponsor system components (e.g., probe) should be removed intact and 
returned promptly to Sponsor for analysis.   
 
11.0 
PROTOCOL DEVIATIONS/MODIFICATION 
 
An Investigator is required to conduct this study in accordance with the signed Investigator's 
Agreement, this investigational protocol, applicable laws and regulations, and any conditions of 
approval imposed by the reviewing IRB/MEC. 
 
The Investigator shall notify the Sponsor and the reviewing IRB/MEC of any deviation from the 
investigational plan to protect the life or physical well-being of a subject in an emergency.  Such notice 
shall be given as soon as possible, but no later than five working days after the emergency occurred.  
Except in such an emergency, prior approval by the Sponsor is required for a change in or deviations 
from this plan and, if these changes or deviations could affect the scientific soundness of the plan or the 
rights, safety or welfare of human subjects, IRB/MEC and national authority approval is also required. 
 
All deviations from the investigational plan must be reported to Sponsor, together with the reason for 
the deviation.  In some circumstances, the center may be required to notify the center’s IRB/MEC and 
Sponsor will notify the national authorities and/or suspend the center’s participation in this clinical 
trial.  In these circumstances, Sponsor will perform a compliance visit to evaluate adherence to the 
investigational plan, compliance with applicable regulations, and any additional specific issues related 
to the event.  Additional training on the protocol and related procedures may also be necessary.  At this 
time Sponsor will ask the Investigator to review the Investigator Agreement and applicable regulations 
regarding medical device clinical studies, specifically Investigator responsibilities. 

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12.0 
DATA QUALITY ASSURANCE 
 
12.1 
Required Data 
 
All required data for this trial will be collected on standardized case report forms (CRFs) designed 
specifically for the study.  In general, the CRFs will be completed by a trained clinical research 
coordinator at the investigational site. Worksheets may be used to collect information that is not 
commonly recorded in medical records. Otherwise, all data should be corroborated by clinic or hospital 
records. Source documents must be available for review during monitoring visits.  In the case of patient 
questionnaires, the CRF may be completed by the subject or the subject may complete a worksheet 
with the data then being transferred to a CRF by the clinical research coordinator, depending on the 
accepted practice at the site. 
 
12.2 
Monitoring Procedures 
 
The study will be administered by the Department of Otolaryngology at the Medical University of 
South Carolina, and two other sites to be determined, and will require approval and monitoring by the 
sponsor.   
 
Each site will allow Olympus Winter & Ibe, the Sponsor of the study and an independent CRO, to 
monitor the study activities and records to ensure that all investigators are in compliance with 1) 
appropriate regulatory requirements, 2) recommendations guiding physicians in biomedical research 
involving human subjects adopted by the 18th World Medical Assembly, Helsinki, Finland, 1964 and 
later revisions, 3) the protocol, and 4) the investigator’s agreement. 
 
Study sites will be monitored to ensure completed case report forms match the Sponsors records and to 
resolve any differences. Original source-documents will be kept in patient charts at the investigator’s 
site and will be available for verification during monitoring or regulatory agency audit.   
The monitor’s responsibilities include: maintaining regular contact with each investigational site, 
through telephone contact and on-site visits, to ensure that the investigational plan is followed; that 
complete, timely and accurate data are submitted; that problems with inconsistent and incomplete data 
are addressed; and that the site facilities continue to be adequate.  
The Sponsor will review significant new information, including unanticipated adverse events, and 
ensure that such information is provided to the investigators, and IRB’s, as appropriate. 
 
The Investigator(s) will ensure that an informed consent form is signed by each patient prior to study 
enrollment. Informed consents will be obtained according to individual institutional guidelines. These 
documents will be audited to ensure they have been signed prior to the RFA procedure and that the 
correct version was used. 
 
Standardized case report forms must be completed for all patients enrolled into the study. Completion 
of standard case report forms will be required by all participating centers. The case report form should 
be a complete and accurate record of the patient’s data collected during the study according to GCP 
recommendations. It is the responsibility of the investigator to ensure the quality of the data collected 
and recorded. 

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The case report forms will be reviewed for errors, omissions, internal consistency, and to ensure that 
the investigator has signed and dated the appropriate sections. Data entry will be done in a manner to 
ensure accuracy and the entered data will be audited for verification and validation purposes. 
 
12.3 
Patient Data Protection 
 
All information and data concerning patients or their participation in this trial will be considered 
confidential. Only authorized personnel will have access to these confidential files. All data used in the 
analysis and reporting of this study will be without identifiable reference to the patients. 
 
12.4 
Ethical and Regulatory Considerations 
 
The study will be performed in accordance with Good Clinical Practices and recommendations guiding 
physicians in biomedical research involving human subjects adopted by the 18th World Medical 
Assembly, Helsinki, Finland, 1964 and later revisions. 
 
The protocol and informed consent will be reviewed and approved before enrollment of patients by the 
appropriate Institutional Review Board where the study will be conducted. 
 
 
13 
ROLES AND RESPONSIBILITIES 
 
13.1 
Role of the Sponsor Representatives  
 
Olympus Winter & Ibe will serve as the Sponsor of this study.  A Sponsor is defined as a person or 
organization that initiates, but does not actually conduct, the investigation (FDA regulation 21 CFR 
812.3(n)). 
Olympus Winter & Ibe personnel may provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during surgical procedures. Support may include HCP 
training, addressing HCP questions, or providing clarifications to HCPs concerning the operation of 
Olympus equipment. 
At the request of the Investigator and while under their supervision, Olympus personnel may assist with 
operation of the equipment during treatment of study subjects. Typical tasks may include: 
x 
Clarifying device setup and  operation as requested by the Investigator or other health care  
personnel 
 
x 
   Observing testing or medical procedures to obtain information relevant to prptocol compliance 
 
Reviewing collected data and study documentation for completeness and accuracy 
Olympus Winter & Ibe personnel will not: 

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x 
Practice medicine 
x 
Provide medical diagnosis  
x 
Independently collect critical study data (defined as primary or secondary endpoint data) 
 
13.2 
Investigator’s Role and Responsibilities 
 
13.2.1 Clinical Investigators 
 
The Investigator is responsible for conducting the study in accordance with the signed agreement, the 
investigational plan, applicable laws, the latest version of the “Declaration of Helsinki: 
Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Patients” and 
any conditions of approval imposed by the reviewing regulatory body.   
 
The clinical investigator shall be responsible for the day to day conduct of the clinical investigation as 
well as for the safety and well-being of the human subjects involved in the clinical investigation. 
 
The clinical investigator shall have the resources to conduct the clinical investigation properly and 
obtain from the sponsor the information which he judges essential about the device and be familiar with 
this information. 
 
The clinical investigator shall ensure that adequate information is given to the subject both in oral and 
written form, on the nature of the clinical investigation. This information shall be easily understandable 
by the subject. This information shall include the aims, expected benefits for him and/or others, risks 
and inconveniences and an explanation of any alternative methods, and of possible consequences of 
any withdrawal from the clinical investigation. Subjects shall be allowed sufficient time to decide 
whether or not they wish to participate. The subjects shall be informed that his/her participation in the 
clinical investigation is completely voluntary and confidential. The subject shall be made aware that the 
data relating to the study may be made available to third parties while maintaining anonymity. 
 
The investigators must obtain a written IRB approval prior to including any patients into the study. 
 
 
13.2.2 Investigator Selection  
 
This study will be conducted by qualified Investigators who have experience with obstructive sleep 
apnea diagnosis and treatment, including knowledge of alternative therapy efficacy. The Investigator 
may have direct experience with the use of CelonProSleep plus.  A principal Investigator and his/her 
sub-Investigator must be experienced in and responsible for: selection and evaluation of patients, strict 
adherence to this investigational protocol, which includes all testing requirements to provide for 
optimal safe and efficacious use of the CelonProSleep plus, collection of patient consent and study 
data, and submission of death letters, notes, etc.; if applicable. 
 
It is acceptable for the Principal Investigator to delegate one or more of the above functions to an 
associate or sub-Investigator who is a trained healthcare professional, and who is trained on the study 

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protocol according to their role in the study.  However, the principal Investigator remains responsible 
for proper conduct of the study.  The study is not transferable to other centers attended by the 
Investigator unless prior approval is obtained from the Sponsor and the appropriate reviewing 
institutional oversight committee and regulatory body as required.  
 
13.3. Study Initiation  
 
Before participating in the clinical trial, each Investigator and sub-Investigator is required to submit to 
Sponsor a signed Investigator's Agreement.  Prior to the Investigator's participation, the Investigator 
must forward written approval from the appropriate reviewing IRB to Sponsor. 
 
13.4 
Clinical Events Committee (CEC) 
 
A Clinical Events Committee, consisting of independent physicians, will review all adverse events at 
regular intervals. The CEC is responsible for reviewing the Investigator’s assessment and classification 
of each event. The CEC will also adjudicate subject withdrawals to determine whether therapy efficacy 
constituted a reason for their withdrawal.  Study withdrawal due to therapy failure will be included in 
primary secondary analysis.   
 
13.5 
Patient Informed Consent 
 
All patients will receive full and adequate verbal and written information and sign the informed consent 
form prior to their inclusion in the study. A copy of the approved informed consent form along with a 
copy of each patient’s signed consent form will be maintained by each investigator in a designated 
clinical study administrative file. A copy of the signed consent form must be given to each patient. 
 
13.6 
Study Termination 
 
The sponsor reserves the right to discontinue the study or a study site at any time. The reason(s) for 
termination shall be discussed with each investigator. Discontinuation shall be effected by fax or 
registered mail. If discontinuation occurs, the appropriate regulatory authorities and the Institutional 
Review Board involved shall be informed in writing within 72 hours after the discontinuation has been 
notified to the Investigators.  Reasons for such action taken by the sponsor include, but are not limited 
to: 
• Successful completion of the trial at the center 
• The required number of subjects for the trial has been recruited 
• Failure of the investigator to comply with the protocol, the sponsor's procedures, or GCP guidelines 
• Safety concerns 
• Sufficient data suggesting lack of efficacy 
• Inadequate recruitment of subjects by the investigator 
 
13.7 
Withdrawal 
 
The only reason for patient withdrawal from this study is patient request. 
 

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13.8 
Protocol Deviations 
 
An Investigator is required to conduct this study in accordance with the signed Investigator's 
Agreement, this investigational protocol, applicable laws and regulations, and any conditions of 
approval imposed by the reviewing IRB. 
 
An Investigator shall notify the Sponsor and the reviewing IRB of any deviation from the 
investigational plan to protect the life or physical well-being of a subject in an emergency.  Such notice 
shall be given as soon as possible, but no later than five working days after the emergency occurred.  
Except in such an emergency, prior approval by the Sponsor is required for a change in or deviations 
from this plan and, if these changes or deviations could affect the scientific soundness of the plan or the 
rights, safety or welfare of human subjects, IRB and national authority approval is also required. 
 
All deviations from the investigational plan must be reported to Sponsor, together with the reason for 
the deviation.  In some circumstances, the center may be required to notify the center’s IRB and 
Sponsor will notify the national authorities and/or suspend the center’s participation in this clinical 
trial.  In these circumstances, Sponsor will perform a compliance visit to evaluate adherence to the 
investigational plan, compliance with applicable regulations, and any additional specific issues related 
to the event.  Additional training on the protocol and related procedures may also be necessary.  Prior 
to continuing involvement in this clinical trial, the results of Sponsor compliance visit and concurrence 
from the center’s IRB and/or national authorities may also be required.  At this time Sponsor will ask 
the Investigator to review the Investigator Agreement and applicable regulations regarding medical 
device clinical studies, specifically Investigator responsibilities. 
 
13.9 
Stopping Rules 
 
If Sponsor makes a decision to discontinue the study (e.g., because of slow enrollment, unanticipated 
adverse event, or other scenario), Sponsor will promptly inform all Investigators, IRB, and relevant 
regulatory authorities; along with detailed information on how enrolled subjects should be managed 
thereafter. All subjects enrolled in this trial will continue to be followed according to the protocol 
unless Sponsor advises otherwise. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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