The Nucleus Hybrid L24 Implant System: Extended Duration Post Approval Study
Phase: NA
Conditions: Hearing Loss
Sponsor: Cochlear

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant 
System _  Version 4 
September 9, 2014  
 
 
 
 
1 
PROTOCOL 
 
Post Approval Study: Extended Duration Monitoring of 
Subjects with the Cochlear™ Nucleus® Hybrid™ L24 
Cochlear Implant System 
 
P130016               
▬▬▬▬▬▬▬▬▬▬▬ 
CAM-5563-HYB-PMA 
Version 4 
September 9, 2014 
▬▬▬▬▬▬▬▬▬ 
Study Sponsor: 
Cochlear Americas 
13059 East Peakview Avenue 
Centennial, CO 80111 
 
 
 
 
 
CONFIDENTIAL - DO NOT COPY 
This protocol contains confidential proprietary information with respect to Cochlear products and 
clinical trials. I agree to hold this information in confidence and not to disclose it to any third 
parties for the shortest of the following periods of time: three years from the date of this 
agreement, the time at which this information becomes a matter of public knowledge, or the time 
at which a formal agreement for that purpose has been entered into by the parties. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
2 
1 Investigator Responsibilities 
I, the undersigned, am responsible for the conduct of the study at the site below and by my 
signature below, I confirm that I have read, understand and will strictly adhere to the study 
protocol, “Post Approval Study: Extended Duration Monitoring of Subjects with the Cochlear 
Nucleus® Hybrid™ L24 Cochlear Implant System.” 
 
 
Clinical Investigational Site 
 
Primary Investigator’s Name (print) 
 
Title 
 
Signature 
 
Sponsor Representative 
 
Title 
 
Signature 
 
 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
3 
2 Table of Contents 
1 
Investigator Responsibilities ................................................................................. 2 
2 
Table of Contents .................................................................................................... 3 
3 
Clinical Investigational Synopsis .......................................................................... 7 
4 
Terms, Definitions, and Abbreviations ................................................................. 8 
5 
Background ........................................................................................................... 10 
5.1 
Regulatory History ........................................................................................... 10 
5.2 
Device Description .......................................................................................... 10 
5.2.1 
Nucleus Hybrid L24 Cochlear Implant ................................................................... 10 
5.2.2 
Nucleus Sound Processor ..................................................................................... 10 
5.2.3 
Acoustic Component ............................................................................................. 11 
5.3 
Custom Sound Clinical Programming Software .............................................. 12 
6 
Indications for Use ................................................................................................ 12 
7 
Purpose of Study .................................................................................................. 13 
8 
Study Objective and Hypothesis ......................................................................... 13 
9 
Study Design ......................................................................................................... 14 
10 Study Population ................................................................................................... 14 
11 Inclusion/Exclusion Criteria ................................................................................. 15 
12 Primary and Secondary Endpoints ..................................................................... 15 
12.1 
Safety Endpoints ............................................................................................. 15 
12.1.1 Primary Safety Endpoint ........................................................................................ 15 
12.1.2 Secondary Safety Endpoint ................................................................................... 16 
12.2 
Co-Primary Efficacy Endpoints ........................................................................ 16 
13 Study Duration ...................................................................................................... 17 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
4 
14 Overview of Study Procedures ............................................................................ 17 
15 Investigational Procedures .................................................................................. 17 
15.1 
Subject Identification ....................................................................................... 18 
15.2 
Release of Medical Information ....................................................................... 18 
15.3 
Informed Consent ............................................................................................ 18 
15.4 
Description of Test Measures .......................................................................... 18 
15.4.1 Audiometric Assessment ....................................................................................... 18 
15.4.2 Speech Perception Assessment ........................................................................... 19 
15.4.3 Subjective Questionnaires ..................................................................................... 20 
15.5 
Programming Follow-Up .................................................................................. 20 
15.6 
External Equipment Check .............................................................................. 20 
15.7 
Hearing Aid Verification ................................................................................... 21 
15.8 
Psychophysical and Electrical Impedance Measurements ............................. 21 
15.9 
Interim Evaluation Intervals ............................................................................. 21 
16 Re-Implantation with a Long Electrode ............................................................... 21 
16.1 
Evaluation PRIOR to Re-implantation with a Long Electrode ......................... 21 
16.2 
Evaluation FOLLOWING Re-implantation with a Long Electrode ................... 22 
17 Summary of Study Procedures ............................................................................ 22 
18 Adverse Events ..................................................................................................... 24 
18.1 
Assessment and Reporting of Adverse Events ............................................... 25 
18.1.1 Investigator’s Responsibilities ............................................................................... 25 
18.1.2 Unanticipated Adverse Device Effects .................................................................. 26 
18.1.3 Adverse Event Follow-up ...................................................................................... 26 
18.1.4 Sponsor’s Responsibilities .................................................................................... 26 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
5 
19 Protocol Deviations .............................................................................................. 26 
20 Study Completion ................................................................................................. 27 
20.1 
Completed Subjects ........................................................................................ 27 
20.2 
Discontinued Subjects ..................................................................................... 27 
20.3 
Premature Study Termination ......................................................................... 28 
21 Study Milestones/Timeline ................................................................................... 28 
22 Data Analyses ........................................................................................................ 28 
23 Sample Size Calculation ....................................................................................... 29 
23.1 
Analysis of Safety ............................................................................................ 29 
23.2 
Analysis of Efficacy ......................................................................................... 29 
23.3 
Annual Review of Subject Characteristics ....................................................... 30 
24 Risk Benefit Statement ......................................................................................... 30 
25 Good Clinical Practices Statement ...................................................................... 31 
26 Access to Study Documents and Study Monitoring .......................................... 32 
27 Quality Control and Assurance ........................................................................... 32 
28 Institutional Review Board ................................................................................... 32 
29 Informed Consent Process .................................................................................. 32 
30 Confidentiality ....................................................................................................... 33 
31 Protocol Amendments .......................................................................................... 33 
32 Data Management ................................................................................................. 33 
33 Record Keeping and Retention ............................................................................ 34 
34 Reporting Requirements for Interim and Final Reports .................................... 36 
35 References ............................................................................................................. 36 
36 Appendix A: Procedural considerations ............................................................. 38 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
6 
37 Appendix B: Instructions for Masking ................................................................ 39 
38 Appendix C: Hearing Aid Fitting Guidelines ...................................................... 40 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
7 
3 Clinical Investigational Synopsis 
 
Title 
 
Post Approval Study: Extended Duration Monitoring of Subjects 
with the Cochlear  Nucleus® Hybrid™ L24 Cochlear Implant 
System 
 
Study Sites 
 
Up to 10 sites from the pivotal IDE (G070191) 
Study Duration 
 
3-5 years 
Study Time 
 
5 years post-activation for each subject 
Study Population 
Up to 35 subjects from the original pivotal IDE (G070191) and 
associated Continued Access IDE supplement who remain implanted 
with Hybrid L24 Implant, enrolled in the study, and have not met their 5 
year post-activation interval as of the date of this submission 
 
Design Overview 
A prospective, multicenter, non-controlled, non-randomized study  
 
Primary Objective 
To evaluate the long term safety and effectiveness of the Nucleus 
Hybrid L24 Implant in implanted subjects out to 5 years post-activation 
 
Study Intervals 
Baseline2 years post-activation (if not yet completed) 
3 years post-activation (if not yet completed) 
4 years post-activation (if not yet completed) 
5 years post-activation (if not yet completed) 
 
Primary Safety 
Endpoint 
Report of medical/surgical and device related adverse events 
consistent with those from the pivotal IDE with regard to type, 
frequency and seriousness  
 
Primary Effectiveness 
Endpoint 
Report of clinical performance using an open set monosyllabic word 
recognition measure in quiet and open set sentence measure in noise 
over the 5 year study period 
 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
8 
4 Terms, Definitions, and Abbreviations 
 
Term/Abbreviation 
Definition 
Acoustic Stimulation 
Pre- or postoperative condition referring to the use of acoustic 
hearing alone, with or without amplification 
Acoustic Component (AC) 
An optional component for the sound processor used with the 
Hybrid L24 implant which provides amplification in the low 
frequencies for those patients who have residual hearing 
sensitivity postoperatively 
AzBio Test1 
A sentence level speech recognition test delivered in background 
noise at a predetermined signal to noise ratio 
Bilateral Acoustic 
Stimulation 
Preoperative condition referring to the use of bilateral acoustic 
hearing, with or without amplification 
Bimodal Mode 
Use of acoustic hearing, with or without amplification, in addition 
to electric hearing via a cochlear implant or Hybrid implant in the 
contralateral (opposite) ear.   
BTE 
Behind-The-Ear 
CI 
Cochlear Implant 
CNC Word Recognition 
Test2 
Consonant-Nucleus-Consonant Test:  A monosyllabic word-level 
test given in quiet and calculated both as a word correct score 
and a phoneme correct score 
Cochlear Implant Alone 
Stimulation delivered by the Hybrid L24 implant alone. 
Combined Mode 
Use of acoustic hearing bilaterally, with or without amplification, 
in addition to electric hearing via a cochlear implant or Hybrid L24 
implant 
CRF 
Case Report Form 
Device Use Questionnaire 
(DUQ) 
“In-house” device usability metric, administered to determine 
subjective preference and satisfaction with regards to device use 
in various listening environments 
Electronic Data Capture 
(EDC) 
 
Everyday Listening 
Condition 
Postoperative listening condition referring to either Combined 
Mode or Bimodal Mode  
HL 
Hearing Loss/Hearing Level 
Hybrid Mode 
Combination of acoustic and electric hearing in the same ear 
                                                
1 Spahr, A, Dorman, M., Litvak, L, Van Wie, S, Gifford, R et al. (2012). Development and validation of the 
AzBio sentence lists.  Ear Hear 33(1): 112-117. 
2 Consonant-Nucleus-Consonant Test; Peterson, F.E. & Lehiste, I. (1962). Revised CNC 
lists for auditory tests. Journal of Speech and Hearing Disorders, 27(1): 62-70. 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
9 
MAP 
A program that defines the individualized fitting parameters of 
recipients for a specific coding strategy. 
National Acoustic 
Laboratories (NAL) 
Refers to a procedu8re for appropriately fitting hearing aids 
Nucleus Custom Sound 
Clinical programming software for Nucleus Implant Systems 
Nucleus Sound Processor  
BTE sound processor that is used to provide electric only or 
electric plus acoustic information when used in the Hybrid Mode 
Signal-to-Noise Ratio (SNR) The level relationship (ratio) of the target (signal) to the noise 
(e.g., if the target speech is 65 dBA and the noise is 60 dBA then 
the SNR = +5 dB) 
Speech, Spatial, and 
Qualities of Hearing Scale 
(SSQ) 
A validated metric used  as a self-assessment of hearing in 
everyday life across three hearing domains:  speech hearing, 
spatial hearing, and qualities of sound 
 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
10 
5 Background 
5.1 Regulatory History 
The Hybrid L24 Implant System (P130016) was the subject of a pivotal clinical trial (IDE 
G070191) from 2007-2012.  Data on the 50 subjects enrolled in the study in support of safety 
and efficacy of the device was submitted in June 2013 as part of PMA #130016.  As part of the 
PMA approval, a Post Approval Study to monitor the long-term (5 years) safety and 
effectiveness of the device in this existing cohort of implanted subjects was designed.   
 
5.2 Device Description 
The Nucleus Hybrid L24 cochlear implant system consists of the following core components: 
 
Nucleus Hybrid L24 cochlear implant, 
 
Nucleus Sound Processor, and 
 
Nucleus Custom Sound™ programming software 
 
5.2.1 Nucleus Hybrid L24 Cochlear Implant 
The Nucleus Hybrid L24 Cochlear Implant to be evaluated in this study is the same as that used 
in the pivotal IDE study (#G070191).  There have been no changes to this internal system 
component. 
5.2.2 Nucleus Sound Processor 
The current sound processor to be used in this clinical study, the Cochlear Nucleus 6 Sound 
Processor, is a BTE processor (Figure 1), with a modular design that incorporates a main signal 
processing module (the “sound processor”) with built-in directional microphones, a battery 
module (2 zinc air or rechargeable), radio frequency (RF) coil and coil cable.  This sound 
processor was developed to provide acoustic (optionally) and electrical stimulation to hearing-
impaired candidates who have some low-frequency residual hearing. The Nucleus 6 Sound 
Processor is functionally equivalent to the previous generation Freedom Hybrid Sound 
Processor. It is the commercially available sound processor for recipients of all current Nucleus 
cochlear implants, including the Hybrid L24 implant, at the time of study initiation. 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
11 
 
Figure 1: Labeled components of the Nucleus 6 Sound Processor 
Due to the long duration of follow up required for this Post Approval Study it is possible that new 
sound processor technology may be introduced during the course of this clinical study.  If new 
technology is released, is proven to be functionally equivalent to the Nucleus 6 Sound 
Processor, and demonstrates performance at least as good as that from the Nucleus 6 sound 
processor, subjects may be given the option to upgrade to the new technology as part of this 
investigation.  
 
5.2.3 Acoustic Component 
Acoustic stimulation is delivered via an acoustic module, called the Acoustic Component. The 
Acoustic Component (Figure 2) connects to the sound processor to deliver acoustic 
amplification in a similar way to that from a conventional hearing aid. The retention of the 
Acoustic Component to the ear can be either via a custom earmold or a non-custom dome. 
Programming of the sound processor and the Acoustic Component is achieved via Custom 
Sound™ software. 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
12 
 
 
Figure 2: Nucleus 6 Sound Processor with Acoustic Component. Shown is the dome retention system.  The 
Acoustic Component can also be used with a custom earmold. 
 
5.3 Custom Sound Clinical Programming Software 
Programming of the sound processor is achieved via Custom Sound™ software.  Custom 
Sound permits the characterization of both electric and acoustic parameters required for 
Nucleus 6 Sound Processor programming. The general approach for the electric programming 
is the same as that for traditional cochlear implant recipients except that the software provides 
more flexible frequency boundary assignments for the 22 channels of the Nucleus Hybrid L24 
cochlear implant. The software provides the ability to specify the cut-off frequency at which 
acoustic stimulation ends and electrical stimulation begins. In addition, the software provides a 
user interface for the clinician to program amplification characteristics (gain and maximum 
output, frequency by frequency) for the subject’s low-frequency range of hearing. 
6 Indications for Use 
All subjects met the following indications when enrolled under IDE G070191.  Therefore, this 
section is for informational use only. 
The Cochlear Nucleus Hybrid L24 Implant System is indicated for unilateral use in patients aged 
18 years and older who have residual low frequency hearing sensitivity and severe to profound 
high-frequency sensorineural hearing loss, and who obtain limited benefit from appropriately fit 
bilateral hearing aids. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
13 
 
Typical pre-operative hearing of candidates ranges from normal to moderate hearing 
loss in the low frequencies (thresholds no poorer than 60dB HL up to and including 500 
Hz), with severe to profound mid- to high-frequency hearing loss (threshold average of 
2000, 3000, and 4000 Hz ≥ 75dB HL), and moderately sever to profound mid- to high-
frequency hearing loss (threshold average of 2000, 3000, and 4000 Hz ≥ 60dB HL) in 
the contralateral ear. 
 
The CNC word recognition score will be between 10% and 60% inclusively, in the ear to 
be implanted in the pre-operative aided condition and in the contralateral ear will be 
equal to or better than that of the ear to be implanted but not more than 80% correct. 
 
Prospective candidates should go through a suitable hearing aid trial, unless already 
appropriately fitted with hearing aids.   
A Cochlear Nucleus Hybrid L24 cochlear implant is not indicated for individuals who have the 
following conditions: 
1. Deafness due to lesions of the acoustic nerve or central auditory pathway 
2. Active middle ear disease, with or without tympanic membrane perforation 
3. Absence of cochlear development 
4. A duration of severe to profound hearing loss of 30 years or greater. 
7 Purpose of Study 
The purpose of the Post Approval Study:  Extended Duration Monitoring of Subjects with the 
Cochlear Nucleus Hybrid L24 Cochlear Implant System is to gather long term safety and 
effectiveness data on subjects implanted as part of the pivotal IDE (G070191).  This real world 
experience may allow us to learn about sub-groups of patients, evaluate training programs, and 
further explore the type and frequency of adverse events beyond that which could be captured 
during the original clinical trial. 
 
8 Study Objective and Hypothesis 
The objective of this study is to collect long term (5 years) safety information and measures of 
device effectiveness on those subjects already enrolled in the pivotal Hybrid L24 IDE 
(G070191).    
 
The study hypothesis will be that mean performance with the speech perception measures 
described below will show significant benefit with use of the Hybrid L24 implant, both in the 
implant ear and when using both ears together, over the 5 year study period when compared to 
the preoperative amplification condition.  

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
14 
9 Study Design 
This Post Approval Study - Extended Duration Monitoring of Subjects with the Hybrid L24 
Cochlear Implant System will be conducted as a repeated-measures, single-subject experiment.  
A single-subject research design (in which each subject serves as his or her own control) is 
appropriate since it accommodates the heterogeneity that characterizes hearing-impaired 
populations.  Blinding or masking procedures are not included in the design as this population 
already has the Nucleus Hybrid L24 Implant System.  It is not possible to conceal the presence 
or absence of the implant from device recipients and/or clinical investigators.  To minimize order 
effects and test bias, word and sentence lists assigned to the various test conditions will be 
randomized across conditions, and the order in which test conditions are completed will be 
randomized.  
This protocol is slightly revised from the original protocol under the pivotal IDE.  Some 
measurements and test conditions that will not provide novel information have been removed to 
increase compliance with a 5 year protocol.   
10 Study Population 
Up to 32 subjects from the original pivotal study (G070191) population for the Hybrid L24 
implant will be invited to participate.  These subjects remain enrolled in the study, implanted with 
a Hybrid L24 device and have not reached their 5 year post-activation interval as of the date of 
this submission.  All study subjects will have met the inclusion/exclusion criteria required for 
participation in the pivotal IDE.  An additional group of 3 subjects who were enrolled in the 
Hybrid L24 Cochlear Implant System – Continued Access clinical trial (G070191/S024) will be 
invited to participate in this Post Approval Extended Duration study once the 12 month endpoint 
has been achieved according to the pivotal IDE protocol.   

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
15 
 
 
Figure 1:  Enrolled Hybrid L24 Subjects 
11 Inclusion/Exclusion Criteria 
All subjects currently enrolled in the pivotal IDE study who remain implanted with a Hybrid L24 
Cochlear Implant(G070191) and have not yet reached their 5 year postactivation interval will be 
invited to participate in this Post Approval Study – Extended Duration protocol.  The only 
applicable exclusion criterion that could prevent participation is an unwillingness or inability of 
the subject to comply with all investigational requirements.   
12 Primary and Secondary Endpoints 
12.1 Safety Endpoints 
12.1.1 Primary Safety Endpoint 
The primary safety endpoint will be the comparison of the type and frequency of adverse events 
and serious adverse events occurring over the course of this study up to the 5 year post-
activation interval as compared to the pivotal clinical study (G070191) for the Hybrid L24 
implant. 
1
0
0
0
4
11
5
6
6
3
5
0
2
4
6
8
10
12
3
6
12
18
24
30
36
42
48
54
60
Remaining Hybrid L24 Subjects 
(L24 + LCA)
# of
Subjects
Last Visit Completed (months postactivation)

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
16 
12.1.2 Secondary Safety Endpoint 
Secondary safety endpoints will include the following: 
 
Cumulative Safety Assessment:  Adverse events with start dates prior to initial activation 
and each follow-up time interval will be tabulated. 
 
Procedure-Related Adverse Event Assessment:  Procedure-related events occurring 
during the follow-up period will be tabulated. 
 
Device-Related Adverse Event Assessment:  Device-related events occurring during the 
follow-up period will be tabulated. 
 
The above two classes of events (procedure and device related) will be summarized as 
rates.  The numerator for each rate will be the number of subjects with at least one 
procedure (or device) related adverse event.  The denominator will be the total number 
of subjects.   
 
Rates (overall and procedure and device related) will also be summarized by type. 
 
Time to first adverse event (including total losses of residual hearing) will be summarized 
using Kaplan Meier plots. Exploratory proportional hazards regression models will be 
used to determine whether demographics and baseline characteristics are associated 
with risk for adverse events over follow-up. Hazard ratios and 95% confidence intervals 
for these analyses will be cited. 
 
12.2 Co-Primary Efficacy Endpoints 
The co-primary efficacy endpoints for this study will be the assessment of statistical significance 
of the within-subject differences for two speech recognition tests, measured in two conditions:  
the implant ear and both ears: 
 
Word recognition in quiet as evaluated with the Consonant-Nucleus-Consonant (CNC) 
test (Peterson and Lehiste, 1962); 
 
Sentence recognition in noise (+5dB SNR) as evaluated with the AzBio test (Spahr et al., 
2011) 
Scores on both speech tests will be obtained at the study baseline (time of enrollment) and 
annually thereafter until study completion, 5 years from the initial activation of the device.   
In an attempt to standardize speech assessment methods across commercial implanting 
centers, the above metrics were chosen based on the Minimum Speech Test Battery (MSTB) 
published in 2011 as a joint effort of the cochlear implant industry and the audiologic/otologic 
professional community.  These test materials are provided free of charge to any cochlear 
implanting center and include calibration and instructions for use.  
A secondary effectiveness analysis will be performed on the per-protocol population, which 
includes all randomized subjects who completed 5 years of follow-up with no major protocol 
violations. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
17 
  
13 Study Duration 
Subjects will be followed to a point in time corresponding to 5 years post initial activation of the 
Hybrid L24 cochlear implant system.  The majority of subjects who enroll in this study will have 
already met a number of data intervals past the 6 month primary end point in the pivotal IDE.  
Therefore, after a baseline evaluation, which will be completed for all enrolled subjects from the 
pivotal IDE who consent to participate regardless of their current time post initial activation, each 
subject will start at the appropriate test interval relative to his or her own initial activation date.  
The total expected duration of this study is 3-5 years which includes time for all enrolled 
subjects to reach their 5 year post-initial activation endpoint.  The target retention rate is at least 
80% at 5 years.  All efforts will be put forth to ensure near complete follow-up, with particular 
focus on assessment of the primary outcome and occurrence of adverse events.  Regular 
reminders of subject follow up due dates will be provided to participating centers to facilitate 
scheduling of follow-up visits.  In the event that a follow up due date is missed, the Sponsor will 
instruct the participating center to make three attempts to contact the study subject and inform 
them of the need to be tested.  The third and final attempt will be in writing and if not response is 
received then the subject will be considered lost to follow up.   
14 Overview of Study Procedures 
Speech perception testing will be completed using the implant ear (hybrid mode or electric only) 
and both ears together (combined or bimodal mode).  The specific test mode will depend on 
whether a subject has retained functional residual acoustic hearing sensitivity.  In addition, 
subjects will be asked to complete subjective questionnaires to measure device use and 
satisfaction, and the degree of preservation of low-frequency hearing will be assessed as part of 
the safety data at each study interval. 
Subjects will remain in the study for five years or until the Sponsor formally closes the study.  
Non-study follow-up evaluations may also take place at the discretion of the study site as part of 
routine care (e.g., to address device programming needs). 
This protocol is slightly revised from the original protocol under the pivotal IDE.  Some 
measurements and test conditions that are considered to not provide novel information have 
been removed to increase compliance with a 5 year protocol. 
 
15 Investigational Procedures 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
18 
15.1 Subject Identification 
To maintain confidentiality, the subject’s name will not be recorded on any study document 
other than the Informed Consent Form.  All individuals who provide informed consent (who sign 
the Informed Consent form), are considered to be consented into the study and will use the 
unique identifier assigned to them.  A unique alphanumeric code will identify the subject 
throughout the course of the study.  For example, US01-HED-0000, where: 
o US = United States  
o 01 = a sequential number corresponding to the order in which a subject is 
enrolled into the study for a given study site 
o HED = an abbreviation for the study, in this case HED for Hybrid Extended 
Duration 
o 0000 = a unique, numeric study site identification 
15.2 Release of Medical Information 
The subject must sign a release that authorizes access of medical records to the study sponsor, 
investigators, monitors, and the Food and Drug Administration (FDA), prior to proceeding with 
any screening evaluations. 
 
15.3 Informed Consent  
The risks and benefits of participating in this study shall be explained to the subject as outlined 
on the Informed Consent Form.  After reviewing the Informed Consent Form the potential 
subject will be given the opportunity to ask questions about the Informed Consent Form and/or 
the study prior to signing.  The subject will then be given a copy of the signed Informed Consent 
Form.   
Note: The Informed Consent document must be reviewed and signed by the relevant parties 
prior to any study-related evaluation taking place. Testing completed as part of normal clinical 
practice, such as the audiogram, is acceptable. However, such testing must be completed per 
the requirements laid out in the Procedures Manual and/or Case Report Forms (e.g., threshold 
measurement at inter-octave frequencies). 
 
15.4 Description of Test Measures 
15.4.1 Audiometric Assessment 
Unaided audiometric thresholds will be obtained for each ear, with insert earphones, using the 
standard audiometric technique for pure-tone air conduction testing (refer to Appendix A for 
required specifications and calibration requirements).   
 
Testing, for both ears, will include the following: 
 
Air conduction thresholds:  125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, 
8000Hz; 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
19 
 
Bone conduction thresholds:  250, 500, 750, 1000, 1500, 2000, 4000Hz 
 
Note:  Clinician will need to confirm the subject’s response to any pure tone stimulus 
presented at 125 and 250Hz as auditory “heard” versus vibrotactile “felt” and record 
the response accordingly. 
 
If the subject demonstrates preserved low frequency hearing in the implanted ear aided 
audiometric thresholds will be obtained for each ear in the sound field using narrow band noise 
and the standard audiometric technique with the speakers positioned at 0° azimuth relative to 
the subject’s head. 
 
 
 
Aided thresholds at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000Hz 
 
Tympanometry in each ear 
 
If any significant change in unaided thresholds is noted then the amplification fitting(s) should be 
re-evaluated and adjustments made if necessary.  A significant change for this purpose only is 
defined as a shift of more than 10dB (for the better or worse) at two or more aidable (i.e., those 
frequencies where thresholds are < 90dB HL) frequencies. 
 
Note:  As these subjects may have measureable low-frequency hearing, it is important that 
appropriate consideration be made for masking or plugging the contralateral ear during 
unilateral testing in the sound field.  See Appendix B for details on masking procedure. 
 
15.4.2 Speech Perception Assessment 
15.4.2.1 Consonant-Nucleus-Consonant (CNC) Word Recognition Test 
The CNC Word Test (Peterson & Lehiste, 1962) is a validated test used clinically and in 
research to assess the performance of adults with hearing aids or cochlear implants on open-
set word recognition ability.  The test consists of 10 recorded lists of 50 monosyllabic words in 
CD format.  For this study, two lists will be administered in quiet at a level equal to 60 dBA in the 
sound field and scored as a total number of words correct, which will be expressed as a 
percentage correct for this study.  Subjects will be tested using a configuration of speech at 0° 
azimuth. 
15.4.2.2 AzBio Sentence Test 
The AzBio Sentence Test (Spahr et al, 2012) is a validated test used clinically and in research 
to assess the open-set sentence recognition in speech-spectrum noise of adults with hearing 
aids or cochlear implants.  It consists of 15 lists of 20 sentences each.  AzBio sentences are 
spoken by different talkers in a conversational style with limited contextual cues that the listener 
can use to predict or ‘fill in’ unintelligible words.  The sentences will be presented at a fixed level 
(65 dBA) in speech weighted noise at a fixed signal-to-noise ratio (+5 dB).  Each list includes 5 
sentences from each of 4 different male and female talkers.   The average level of intelligibility 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
20 
of each list is 85% +/- 1%.  Each word in the sentence counts towards the overall score.  
Subjects will be tested using a configuration of speech and noise at 0° azimuth.  
15.4.2.3 Test conditions 
The following test conditions will be assessed for both CNC in quiet and AzBio in noise: 
1. Implant  (Hybrid mode or CI alone) 
2. Everyday (Hybrid + Contralateral Acoustic or Bimodal) 
 
Each subject’s default MAP parameters, including rate of stimulation, number of maxima, and 
pulse width will be maintained for testing.  The default Everyday signal processing algorithms 
(ASC +ADRO) will be utilized with all other signal processing algorithms turned off. 
 
15.4.3 Subjective Questionnaires 
15.4.3.1 Speech Spatial and Qualities of Speech Questionnaire (SSQ) 
The SSQ (Gatehouse & Noble, 2004) will be used as a subject self-assessment in three 
categories (speech hearing rating scale, spatial rating scale, and sound qualities rating scale). 
The SSQ is considered a closed-ended self-report assessment of outcome. 
15.4.3.2 Device Use Questionnaire (DUQ) 
This questionnaire was developed by the Sponsor for use in the pivotal IDE and is used to 
collect information regarding device usability, subjective preferences, and satisfaction with 
regards to device use in various listening conditions. 
 
15.5 Programming Follow-Up 
The basic programming approach will be to assign frequency channels to the Hybrid electrode 
array that supplement the acoustic sensitivity.  In other words, the frequency assignment of the 
electrical stimulation will begin at the frequency where acoustic hearing is no longer useful.  For 
this purpose, hearing thresholds above 85dB HL will be considered not useful from an 
amplification perspective and not aidable acoustically.  For example, if the subject’s hearing in 
the implanted ear is more than 85 dB HL for frequencies at and above 1000 Hz (i.e., useful 
acoustic hearing up to 750 Hz), the lower frequency boundary for electric stimulation will be set 
as close as possible to 750 Hz (i.e., the last aidable frequency).  That is, electrical stimulation 
would be provided in this case for inputs from around 750 to 8000 Hz and acoustic for 
frequencies at and below 750 Hz. 
15.6 External Equipment Check 
Prior to any speech perception testing, an assessment of the external hardware, including the 
Sound Processor and Acoustic Component, will be made.  If any clinically significant change in 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
21 
unaided thresholds is noted then the amplification fitting(s) will be re-evaluated and adjustments 
made if necessary. 
15.7 Hearing Aid Verification 
A hearing aid check will be completed by the clinician to verify that the contralateral hearing aid 
and the Acoustic Component for the Nucleus 6 Sound Processor in the implanted ear, if used, 
are functioning prior to aided testing.   
If any significant change in unaided thresholds is noted then the amplification fitting(s) should be 
re-evaluated and adjustments made if necessary.  As noted above, significant change for this 
purpose only is defined as a shift of more than 10dB (for the better or worse) at two or more 
aidable (i.e., those frequencies where threshold are < 90dB HL) frequencies.  See Appendix C 
for additional information on fitting the contralateral hearing aid. 
15.8 Psychophysical and Electrical Impedance Measurements 
The following routine psychophysical and electrical impedance measurements will be obtained 
at the baseline evaluation as well as all annual post-activation intervals up to and including 5 
years. 
1. Electrical thresholds measured in Current Level on at least 5 channels per the 
streamlined fitting method 
2. Electrical maximum comfort levels measured in Current Level on at least 5 channels 
3. Impedance telemetry results using common ground (CG) and monopolar (MP1, MP2, 
and MP1+2) stimulation modes. 
 
15.9 Interim Evaluation Intervals 
Should a subject report a decrement in performance and should that decrement in performance 
not be directly related to a simple hardware problem, all specified interval testing will be 
conducted.  Additionally, an otologic/medial case history will be taken.   
16 Re-Implantation with a Long Electrode 
16.1 Evaluation PRIOR to Re-implantation with a Long Electrode 
As of July 8, 2014 six of the fifty subjects implanted under the pivotal IDE have elected to have 
the Nucleus Hybrid L24 cochlear implant removed and replaced with a standard, long electrode 
array cochlear implant.  This has typically been in cases where individuals have experienced a 
profound or complete loss of residual hearing.  Information about these six individuals has 
previously been reported to the FDA at the ENT Devices Panel meeting held on November 8, 
2013.  There have been no additional explantations since that time.   

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
22 
In order to ensure that accurate information is gathered for any subject electing to undergo 
explantation and re-implantation with a long array, additional data will be collected prior to re-
implantation.  This evaluation will include the following information and will follow the procedures 
described in the annual evaluation schedule:  
 
Audiometric testing 
 
Speech perception testing 
 
Psychophysical and electrical impedance measurements 
 
Otologic/medical questionnaire 
If explantation occurs, in addition to being considered an anticipated serious adverse event, an 
MDR will be filed per 21 CFR Part 803. 
16.2 Evaluation FOLLOWING Re-implantation with a Long Electrode 
Subjects who elect to be implanted with a standard cochlear implant in the test ear in place of 
the Nucleus Hybrid L24 cochlear implant will be required to complete the study protocol as 
outline above.  That is, they will be asked to follow the same postoperative schedule and 
procedures up to their 5 year post-activation interval.   
17 Summary of Study Procedures 
The following procedures will be completed at the baseline evaluation and then annually 
thereafter until the subject reaches the 5 year post-activation interval.  Subjects who have 
already reached the 5 year interval will be seen for a one-time baseline evaluation where these 
same measures will be collected: 
 
Hearing aid verification and external equipment check 
 
Standard unaided audiometric threshold measures (insert earphones), for both ears 
 
Aided audiometric thresholds (implant ear) 
 
Tympanometry 
 
Speech perception testing for the implant ear alone and both ears together 
o CNC word recognition test in quiet at 60 dBA 
o AzBio sentences at 65 dBA in noise (+5 dB SNR)  
 
Subjective questionnaires of benefit 
o SSQ 
o DUQ 
 
Psychophysical measures and electrical impedance measures 
 
Impedance telemetry results using common ground (CG) and monopolar (MP1, MP2, 
and MP1+2) stimulation modes 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
23 
 
 
Table 1:  Summary of Data Collection Visits 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
Evaluation 
 
 
2 Years 
Post IA 
 
3 years 
Post IA 
 
4 Years 
Post IA 
 
 
5 Years 
Post IA 
Informed 
Consent 
X 
 
 
 
 
HA Check/ AC 
Verification 
X 
X 
X 
X 
X 
Unaided 
Hearing 
Thresholds  
X 
X 
X 
X 
X 
Tympanometry 
X 
X 
X 
X 
X 
Aided 
Audiometric 
Thresholds 
X 
X* 
X* 
X* 
X* 
Processor 
Hardware 
Check 
X 
X 
X 
X 
X 
CNC test 
(Implant Ear 
and Both Ears) 
X 
X 
X 
X 
X 
AzBio-at +5dB  
SNR (Implant 
Ear and Both 
Ears) 
X 
X 
X 
X 
X 
DUQ 
X 
X 
X 
X 
X 
SSQ 
X 
X 
X 
X 
X 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
24 
*Note:  Aided audiometric thresholds will be required at each annual interval so long as unaided 
hearing has been preserved at the time of testing. 
 
18 Adverse Events 
For purposes of this protocol, Adverse Events (AE) reporting will be consistent with complaint 
reporting for similar approved technologies under 21 CFR 820.198 as the Nucleus Hybrid L24 
cochlear implant is an approved device.  The sponsor expects an increase in the percent of AEs 
reported per the installed base given the required reporting under this protocol.  
As for loss of hearing sensitivity at the implant ear, these data will be trended in a similar fashion 
to the pivotal protocol (G070191) but will not be considered an adverse event unless the loss 
reaches a profound level (PTA average of 90 dB or greater for frequencies 125-1000Hz), total 
loss and/or explantation. Should an explantation occur, the sponsor will treat this as a serious 
injury with reporting occurring under the Medical Device Reporting regulations (21 CFR Part 
803) in addition to inclusion in the annual update report on the Post Approval Study.  
An Adverse Event (aka Adverse Effect or AE) is the development of an untoward medical 
occurrence or the deterioration of a pre-existing medical condition following or during exposure 
to an investigational product, whether or not considered causally related to the product or the 
surgical procedure to implant it.  An untoward medical condition can be symptoms (e.g., 
nausea), signs (e.g., tachycardia, fever) or clinically significant abnormal results of an 
investigation (e.g., laboratory findings, chest x-ray). 
Adverse events that occur during this study may be associated with the implant procedure, 
including those from general anesthesia, or specifically associated with the use of the device.  
An adverse event will be considered to be device-related when, in the judgment of the Primary 
Investigator, there is a logical connection between the use of the device and the occurrence of 
the event, above and beyond the study procedure itself.  Adverse events associated with 
cochlear implantation in previous investigations include tinnitus, dizziness, swelling, facial nerve 
stimulation, and open and/or short circuit electrodes, among others. 
A Serious Adverse Event (SAE) is any untoward medical occurrence which: 
 
Results in death; 
 
Is life-threatening; 
 
Requires in-patient hospitalization for > 24 hours or prolongation of hospitalization 
which is not specifically required by the protocol; 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
25 
 
Results in permanent impairment of a body function or permanent damage to a body 
structure; or 
 
Requires medical or surgical intervention to preclude permanent impairment of a 
body function or permanent damage to a body structure. 
For any SAEs, if the Primary Investigator judges that  there is a logical connection (caused or 
contributed to) between the use of the device and the occurrence of the event, the event will be 
evaluated for reporting requirements under 21 CFR 803 and reported as an MDR if applicable.   
An unanticipated adverse device effect (UADE) is “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 investigational plan 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” [FDA 21 CFR 812.3(s)].  The Sponsor will promptly conduct an investigation 
upon notification by an Investigator of a UADE and will notify the FDA and all reviewing IRBs 
and participating Investigators within 10 working days after the sponsor first receives notice of 
the effect. Thereafter, the Sponsor will submit such additional report concerning the effect as 
requested by the FDA. 
. 
18.1 Assessment and Reporting of Adverse Events 
18.1.1 Investigator’s Responsibilities 
Throughout the course of the study, all efforts will be made by the Investigators to remain alert 
to possible AEs. The first concern will be the safety and welfare of the subject and for providing 
appropriate medical intervention, as indicated. Detailed information regarding adverse events 
(AEs) will be recorded by the Investigator at the time an adverse event occurs using an Adverse 
Event Questionnaire, provided as part of the Case Report Forms (CRFs) for the study. All 
adverse events will be recorded from the day of enrollment (Day 0) to termination of study or 
when the subject exits the study, whichever is last, even if the event was acknowledged as a 
risk factor in the Informed Consent Form. 
AEs will be recorded on an Adverse Event Questionnaire and will include the following 
information: 
 
Date of onset 
 
Date reported to the investigational site 
 
Description of the AE 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
26 
 
Seriousness 
 
Investigator’s assessment of the relationship of the AE to the device and/or procedure 
 
Treatment 
 
Outcome 
 
18.1.2 Unanticipated Adverse Device Effects 
Unanticipated adverse device effects (UADEs) must be reported directly to the clinical center’s 
reviewing IRB and the Sponsor, Cochlear Americas, within 10 working days of knowledge of the 
event, or as dictated by the specific IRB policy, whichever is sooner. Information regarding the 
UADE will be recorded on the Unanticipated Adverse Device Effect Report, provided with the 
CRFs for the study. 
18.1.3 Adverse Event Follow-up 
All AEs must be followed until resolution, or until the condition stabilizes. The Investigator is 
responsible to ensure that follow-up includes any supplemental investigations as may be 
indicated to elucidate as completely as possible the nature and/or causality of the AE.  This may 
include additional laboratory tests or investigations, or consultation with other health care 
professionals.  Cochlear or its designee may request that the Investigator perform or arrange for 
the conduct of supplemental measurements and/or evaluations.  AE follow up information will be 
recorded using a Follow Up to a Previously Reported Adverse Event Questionnaire, provided 
with the CRFs for the study. 
18.1.4 Sponsor’s Responsibilities 
All AEs will be reported annually to FDA in accordance with the IDE regulation [FDA 21 CFR 
Part 812.150(b)(5)]. All unanticipated adverse device effects (UADEs) will be reported to FDA 
within 10 calendar days of the event in accordance with FDA 21 CFR Part 812.46(b) and 
812.150(b)(1) as well as 21 CFR 803.  
Cochlear Americas or its designee will notify all participating Investigators of any new 
information that alters the current risk-benefit assessment of the study device or that would be 
sufficient to consider changes in management of the Nucleus Hybrid L24 cochlear implant or in 
the overall conduct of the trial. 
19 Protocol Deviations 
A protocol deviation refers to a study-related activity that is not in compliance with the 
investigational protocol.  Deviations that are required to protect the life or well-being of a subject 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
27 
do not require prior approval from the Sponsor and should be implemented immediately.  In 
these cases, the deviation must be reported to the  IRB and Sponsor within 5 (five) days of the 
event. 
If a subject is unable to return for follow-up before the closure of a study visit window (+/- 90 
days for post-activation study visits), or if protocol-defined assessments or parts thereof are 
omitted or completed incorrectly, the event is to be noted on the Protocol Deviation Log 
provided to the Investigator in the study Regulatory Binder.  Depending on the type or severity 
of the deviation the Investigator may be required to notify the IRB and/or Sponsor if the 
deviation impacts safety or performance of the subject or data integrity. 
20 Study Completion 
20.1 Completed Subjects 
Each subject in the study will be considered completed when all assessments up to and 
including 5 years post-activation interval have been performed in accordance with the study 
protocol.  To be considered a primary endpoint success, subjects must retain their originally 
implanted device. 
20.2 Discontinued Subjects 
Any subject may voluntarily discontinue the study at any time without prejudice. The Investigator 
may discontinue a subject from the study at any time if (s)he considers that remaining in the 
study compromises the subject’s health or the subject is not sufficiently cooperative. In either 
event, reason(s) for discontinuation should be recorded on a study withdrawal form, provided as 
part of the CRFs for the study.  
Possible reasons for study discontinuation include the following: 
 
AE necessitating discontinuation from the study 
 
The subject is lost to follow-up 
 
Voluntary decision to withdraw consent made by the subject3 
 
Investigator decision4 
                                                
3 Withdrawal of consent is defined as the subject’s voluntary decision to revoke consent to continue 
participation in the study. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
28 
 
Other reason 
In case of a subject lost-to-follow-up, the Investigator must attempt to contact the subject (or 
relative/family contact) by phone, email or letter at least three times. If attempts are 
unsuccessful, the ‘subject withdrawal’ form is to be completed in the study file and reported, as 
appropriate, in required reports to the Sponsor, IRB and FDA. 
20.3 Premature Study Termination 
The Sponsor reserves the right to discontinue the study for any safety, ethical, or administrative 
reason at any time.  Subjects already implanted with the device being studied will continue to be 
supported, independent of any decision made about study continuation. 
21 Study Milestones/Timeline 
 
Expected Date of Study Initiation 
 
 
10/1/2014 
 
Expected Monthly Number of Study Sites with IRB Approval 
 
 
3 
 
Expected Date of Initiation of Subject Enrollment 
 
 
12/1/2014 
 
Expected Number of Subjects Enrolled per Month 
 
 
5 
 
Expected Date for Subject Enrollment Completion 
 
 
7/1/2015 
 
Expected Date for Complete Follow-up for All Study Participants 
 
 
4/1/2019 
 
22 Data Analyses 
                                                                                                                                                          
4 Subject withdrawal from the study is defined as an Investigator decision. The Investigator may elect to 
withdraw a subject from the study at any time if he/she considers that remaining in the study 
compromises the patient’s health or if the Investigator considers the subject lost to follow-up. 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
29 
Detailed Statistical Analysis for this study is addressed in detail in the document entitled 
“Statistical Analysis Plan for Post Approval Study: Extended Duration Monitoring of the Cochlear 
Nucleus Hybrid L24 Implant.” 
23 Sample Size Calculation 
While there will be a parallel study involving a minimum of 100 newly implanted Hybrid L24 
implant subjects in addition to the original pivotal IDE cohort of 50 subjects, safety and efficacy 
data will be available on a minimum of 150 subjects in total.   
For characterizing the incidence of adverse events over time, such as the occurrence of low 
frequency hearing loss, a total of 150 subjects would provide a precision (defined as the half-
width of a two-sided 95% confidence interval) of approximately 8.3% or smaller.  This 
calculation is based on an exact binomial confidence interval.  Additionally, speech performance 
can be well characterized with a cohort of 50 subjects as demonstration in the original Hybrid 
L24 PMA data.  Further, with this planned sample size for the combined cohorts, speech 
performance data on between 50 and 150 subjects will provide a precision of between 4.7% and 
8.2% based on a standard deviation of approximately 29% as observed in the Hybrid L24 PMA 
data for the change in CNC and AzBio scores from preoperative to 6 months.   
 
23.1 Analysis of Safety 
 
Adverse Events and Serious Adverse Events will be expressed as events per patient 
–time.  
 
All adverse event rates will be reported as the number and frequency of events with 
corresponding 95% exact binomial confidence limits and the number of events per 
patient-time (e.g., events per 10 patient years), and compared to the adverse events 
from G07019 (Hybrid L24 pivotal study). 
 
Time to first adverse event (including total losses of residual hearing) will be 
summarized using Kaplan Meier plots. Exploratory proportional hazards regression 
models will be used to determine whether baseline factors are associated with risk 
for adverse events over follow-up. Hazard ratios and 95% confidence intervals for 
these analyses will be cited. 
 
23.2 Analysis of Efficacy 
The significance of the mean differences in speech recognition scores between preoperative 
and the post-implant interval will be analyzed using maximum likelihood based on repeated 
measures linear regression models. In particular, repeated measures mixed models with subject 
as a random effect will be used that accounts for the within-subject correlation, allowing for 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
30 
comparisons between baseline and follow-up co-primary endpoints. The analyses will 
incorporate the available time intervals: baseline, 2 years post initial activation (IA), and annually 
up to 5 years post IA. Follow-up time intervals will be treated as categorical, thus no test score 
trajectory pattern will need to be captured by the models. If there is significant evidence that the 
assumption of normality does not hold (i.e., p < 0.05 from a Shapiro-Wilk test of normality), then 
ranked data will be used in the repeated measures models. 
 
The secondary effectiveness analysis will be performed on the per-protocol population, which 
includes all randomized subjects who completed 5 years of follow-up with no major protocol 
violations. 
 
23.3 Annual Review of Subject Characteristics 
Both  safety and effectiveness data will be reviewed on an annual basis to compare the 
characteristics of subjects who remain enrolled in the study versus those who were lost to follow 
up.  Baseline covariates to be explored and compared with study outcomes, specifically hearing 
loss and effectiveness measures, include: 
 
age at implantation,  
 
gender,  
 
duration of hearing loss, 
 
duration of severe hearing loss, 
 
pre-operative speech perception score,  
 
pre-operative low frequency pure tone average 
 
post-operative speech perception score (CNC and AzBio Sentences) at the last 
evaluation 
 
type and frequency of adverse events  
 
distance from the implant center 
 
24 Risk Benefit Statement  
The Nucleus Hybrid L24 Implant System represents a new treatment option for a patient 
population that has few current therapeutic alternatives for high frequency sensorineural hearing 
loss.   High frequency sound, crucial for speech discrimination, is provided electrically by the 
Hybrid L24 Implant while residual low frequency hearing is amplified by the acoustic component.  
The two modes of stimulation are processed and provided simultaneously by the externally 
worn Nucleus Sound Processor. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
31 
Subjects with high frequency hearing loss that participated in the pivotal Hybrid L24 clinical 
study (G070191) were able to combine both low frequency (acoustic) and high frequency 
(electric) information, from one or both ears, provided by the Hybrid L24 Implant System. 
Results indicated significant speech perception improvements in quiet and in noise when 
compared to preoperative performance. At the primary study endpoint (6 months post 
activation), 100% of subjects showed equal or greater speech perception performance when 
listening with both ears (Hybrid + hearing aid in the opposite ear); greater than or equal to 90% 
of subjects showed equal to or greater speech perception performance when listening in the 
Hybrid Mode (electric and acoustic in the same ear).   
As documented in the pivotal IDE (G070191) study results, a percentage of individuals will lose 
their preoperative low frequency acoustic hearing subsequent to implantation of the Hybrid L24 
Implant.  This known risk is disclosed in the Hybrid L24 implant system labeling and is strongly 
recommended as an integral component of preoperative surgical and device counseling.  
Irrespective of the postoperative hearing status, most individuals can still be expected to receive 
substantial functional and speech recognition benefit on a daily basis when compared to their 
preoperative listening configuration of two hearing aids.  The pivotal IDE study results also 
demonstrated the absence of unreasonable risk of illness or injury associated with the use of 
the device for its intended uses and conditions of use.  
For those subjects consenting to participate in this Post Approval Study the probable benefits to 
health from use of the Hybrid device for its intended uses and conditions of use, when 
accompanied by adequate directions and warnings against unsafe use, outweigh any probable 
risks.  
To characterize the clinical significance of residual low-frequency loss and assess the benefit-
risk profile of the Hybrid L24 implant, an analysis of subjects’ co-primary efficacy endpoints will 
be performed based on splitting subjects by their degree of low frequency hearing loss. This will 
follow the analysis of the Hybrid L24 PMA data with subjects experiencing moderate, 
moderately-severe, or severe low frequency hearing loss (Group 1) and subjects experiencing 
profound or total low frequency hearing loss (Group 2) described separately for their long term 
speech performance. 
25 Good Clinical Practices Statement 
This trial will be conducted in compliance with all applicable U.S. Federal Regulations and Good 
Clinical Practice (GCP) standards. This trial will be conducted in compliance with the protocol as 
approved by the FDA and each Investigative Site’s Institutional Review Board (IRB). Any 
deviations from the protocol will be reported to the Sponsor and in accordance with the IRB’s 
institutional guidelines. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
32 
26 Access to Study Documents and Study Monitoring 
The Sponsor will designate appropriately trained monitors to review the progress of this 
supplemental study and assure the quality and integrity of data accumulated.  Clinical monitors, 
as representatives of the Sponsor, have the obligation to provide site qualification and initiation 
visits as well as regular site visits.  All data generated and the source documents from which 
they originated are open to inspection by the Sponsor or its representative, the FDA, and other 
regulatory agencies. 
27 Quality Control and Assurance 
Sponsor employees and/or their contracted representatives utilize Standard Operating 
Procedures (SOP) designed to ensure that clinical study procedures and documentation are 
consistently conducted/prepared to the highest quality standards.  Safety data adjudication will 
be conducted by the Sponsor’s Chief Medical Officer, in accordance with these SOPs.  These 
SOPs require compliance with federal regulations and Good Clinical Practice guidance.   
28 Institutional Review Board 
Prior to the initiation of the study, the Protocol, the Informed Consent Form, and other 
supporting documentation must be submitted to the Institutional Review Board (IRB) for 
approval after FDA conditional or final approval.  A copy of the IRB approval letter for the 
Protocol, the Informed Consent, and the Investigator Agreement must be submitted to the 
Sponsor prior to the consent of the first subject.  The study site must maintain an accurate and 
complete record of all reports, documents, and other submissions made to the IRB concerning 
this protocol. 
A list of the IRB members, their titles or occupations, and their institutional affiliation, or an IRB 
assurance number and their contact information must be provided to the Sponsor or its 
designee prior to release of study supplies.  Additionally, the Chair of the IRB must be identified. 
FDA/relevant health authority regulations require that all advertisements for subject recruitment 
be approved by an IRB prior to implementation.  The complete text and format must be 
submitted to the Sponsor or its designee for approval prior to IRB submission.   
29 Informed Consent Process 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
33 
It is the responsibility of the Investigator to inform each subject prior to the initial study 
evaluation, of the purpose of this clinical trial, including possible risks and benefits, and 
document the informed consent process in the subject’s chart. 
A sample informed consent form containing the required elements of informed consent is 
provided by the Sponsor to the IRB once FDA approved.  Any changes made to this sample by 
the IRB must be approved by the Sponsor, or its designee, prior to final submission to the IRB.  
After approval by the Sponsor, the final informed consent must be approved by the IRB.  Prior to 
entry into the study or initiation of any study-related procedures, each subject must read, sign, 
and date the informed consent form.  The person executing the consent must also sign and date 
the consent form.  One original informed consent form is to be retained by the study site and a 
copy is to be given to the subject.  
30 Confidentiality 
In accordance with Good Clinical Practices (GCPs) and with the Health Insurance Portability 
and Accountability Act of 1996 (HIPAA) all information concerning the subjects in the study must 
be treated as strictly confidential by all persons involved in the study. 
The Investigator acknowledges that any and all information acquired from the Sponsor or its 
designee or developed or acquired in connection with the study are strictly confidential.  The 
Investigator will not disclose any confidential information to any third party nor use confidential 
information for any purpose without first obtaining the consent of Sponsor in writing.  Such 
consent shall be deemed to have been given for disclosure to any person for whom the 
Investigator is responsible at his/her center, but only so far as required for the purposes of the 
study, and, in the case of disclosures to staff, only if such staff are bound by obligations of 
confidentiality no less strict than those set out herein.    
31 Protocol Amendments 
The Sponsor will document modifications to the protocol in the form of a written amendment.  
Amended protocols must be acknowledged by Investigator signature and date upon receipt.  
Protocol modifications that impact subject safety or the validity of the study must be approved 
by the FDA and IRB before implementation. In the case of a medical emergency, to remove 
immediate apparent hazard to subjects, a change may be made preferably after discussion with 
the Sponsor or its designee. In these instances, the IRB and FDA will be notified as soon as 
possible.  
32 Data Management 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
34 
All study data will be entered into an Electronic Database Capture (EDC) system. Study 
personnel requiring access will have their own Login/Password. Access to clinical study 
information will be based on an individual’s role and responsibilities.  The application provides 
hierarchical user permission for data entry, viewing, and reporting options. For optimum 
security, all communications between the users and the EDC operate on a secured socket layer 
(SSL) using 256-bit encryption. The web servers are protected by a managed firewall from 
potential web and network attacks and the network is guarded by an intrusion detection and 
protection surveillance system against malicious threats. 
As part of the data entry and validation process, the data stored in the EDC is checked against 
the source data, and also against edit check queries to confirm that the data received is within 
expected ranges. If any data is missing or is outside of expected limits, a query is created and 
sent to the site coordinator so that data may be verified and corrected. All changes made to a 
form are stored in an audit trail. 
33 Record Keeping and Retention 
Data generated for the study should be stored in a limited-access file area and be accessible 
only to representatives of the study site, the Sponsor and its representatives, and FDA/relevant 
health authorities/regulatory agencies. All reports and communications relating to study subjects 
will identify subjects only by subject unique identification code. Complete subject identification 
will be kept by the Investigator. This information will be treated with strict adherence to 
professional standards of confidentiality. 
An Investigator must in reasonable time, upon request from any properly authorized officer or 
employee of FDA/relevant health authority or regulatory agency, permit such officer or 
employee to have access to requested records and reports, and copy and verify any records or 
reports made by the Investigator. Upon notification of a visit by the FDA, the Investigator will 
contact the Sponsor or its designee immediately. The Investigator will also grant Sponsor 
representatives the same privileges offered to FDA/relevant health authority or regulatory 
agents/officers/employees. 
The Investigator must provide the Sponsor or its designee with the following documents at the 
time of site qualification and prior to study initiation and retain a copy in the site study file: 
 
Signed and dated curriculum vitae for the Principal Investigator 
 
A copy of the original approval for conducting the study by the IRB. Renewals, with 
continuance of the study, must be submitted at yearly intervals or as required by IRB 
policy and a copy of the approved and dated renewal provided to the Sponsor. 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
35 
 
A copy of the IRB approved informed consent form along with any modifications initiated 
by the Sponsor over the course of the study 
 
An IRB member list and Federal Wide Assurance (FWA) Number 
 
A signed Financial Disclosure Form for each Investigator 
 
An Investigator Agreement for this protocol signed and dated by each Investigator 
In addition to the documents listed above, the study site will also retain the following items and 
make them available for Sponsor review upon request.   
 
Certifications, applicable study equipment (audiometers, etc.) calibration records and 
laboratory reference ranges for all local laboratories used for this study. The Sponsor will 
verify all equipment requirements at the study qualification and/or initiation. Sites with 
outdated and/or non-compliant equipment will either not be approved for study 
participation or will be advised to discontinue study-related activities should non-
compliance be noted during regular study monitoring visits. 
 
All original informed consent forms with required signatures 
 
All IRB correspondence (i.e., informed consent [including any approved revisions], 
protocol, AEs, advertisements, newsletters) 
 
Copy of the Study Monitoring Log Sheet 
 
Clinical and non-clinical supply shipment forms and device accountability logs 
 
Copies of all correspondence pertaining to the study between Sponsor and the site 
 
Copies of all SAEs reports submitted to the Sponsor 
 
Copies of all FDA progress reports submitted to the site by the Sponsor 
 
Site Delegation Signature Log 
All study-related records must be maintained for at least 2 years after a marketing application 
(PMA) is approved for the study device; or if the application is not approved, until at least 2 
years after shipment and delivery of the last device for investigational use is discontinued and 
FDA/health authorities or regulatory agencies have been notified of study closure. The Sponsor 
will notify the principal Investigator when records are no longer needed. The Investigator will not 
discard any records without notifying the Sponsor. If the Principal Investigator moves from the 
current investigational site, the Sponsor should be notified of the name of the person who will 
assume responsibility for maintenance of the records at the investigational site or the new 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
36 
address at which the records will be stored. The Investigator will notify the Sponsor as soon as 
possible in the event of accidental loss or destruction of any study documentation. 
34 Reporting Requirements for Interim and Final Reports 
Interim Post Approval Study Status Reports will be submitted to the FDA every 6 months for the 
first two years of the study and annually, thereafter.  This schedule will continue for the duration 
of the study until the Final Post-Approval Study Report to be filed within 3 months after study 
completion. 
 
Study Report and Publication 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. 
The aggregate data resulting from this study will be the proprietary information of the Sponsor 
and may be made public after all data have been analyzed and the study results are available.  
None of the data resulting from this study will be allowed to be presented or published in any 
form, by the Investigator or any other person, without the prior written approval of the Sponsor.  
At the end of the study, a clinical study report will be written by the study Investigators or their 
designee and reviewed by the Sponsor. 
 
35 References 
Byrne, D., Parkinson, A., & Newall, P. (1990). Hearing aid gain and frequency response 
requirements for the severely/profoundly hearing-impaired. Ear and Hearing, 11, 40-49. 
Ching, T., Dillon, H., & Byrne, D. (1998). Speech recognition of hearing-impaired listeners: 
predictions from audibility and the limited role of high-frequency amplification. Journal of 
Acoustic Society of America, 103, 1128-1140.  
Dillon, H. (1999). NAL-NL1: A new prescriptive fitting procedure for non-linear hearing aids. The 
Hearing Journal, 52(4), 10-16. 
Furlong WJ, Feeny DH, Torrance GW, Barr RD.(2001) The Health Utilities Index (HUI) system 
for assessing health-related quality of life in clinical studies. Ann Med. 2001 Jul;33(5):375-84. 
Hogan, C. & Turner, CW. (1998). High-frequency amplification: benefits for hearing-impaired 
listeners. Journal of Acoustic Society of America, 104, 432-441.  

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
37 
Minimum Speech Test Battery (MSTB), (2011).  
Noble, W. & Gatehouse, S. (2004). The Speech, Spatial and Qualities of Hearing Scale (SSQ). 
International Journal of Audiology, 43(2), 85-99. 
Peterson,GE & Lehiste I.(1962) Revised CNC lists for auditory tests. J Speech Hearing 
Disorders  27:62-70 
Robinson K, Gatehouse S & Browning GG (1996) Measuring patient benefit from 
otorhinolaryngological surgery and therapy. Annals of Otology, Rhinology and Laryngology, 105: 
415:422 
Spahr AJ, Dorman MF, Litvak LL, Van Wie S, Gifford RH, Loizou PC, Loiselle LM, Oakes T, 
Cook S. (2012) Development and Validation of the AzBio  Sentence Lists. Ear and Hearing  
33:112-7. 
Turner, C.W. (2006). Hearing loss and the limits of amplification. Audiology & Neurotology, 11 
(suppl), 2-5. 
Turner, C.W. & Brus, S.L. (2001). Providing low and mid-frequency speech information to 
listeners with sensorineural hearing loss. Journal of Acoustic Society of America, 109, 2999-
3006.  
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
38 
36 Appendix A: Procedural considerations 
 
All pre and postimplantation testing will be completed using an audiometer, such as a 
Grason Stadler GSI 61 (Grason Stadler, Inc., Milford, NH, U.S.A.) or equivalent, 
calibrated to American National Standards Institute (ANSI) standards with maximum 
output for frequencies of 0.5 to 4 kHz of no less than 120 dB HL. 
 
Speech and hearing evaluations will be completed in, at a minimum, a single-walled 
sound booth capable of accommodating a calibrated, 90-degree, speaker orientation. 
 
Stimuli will be administered using either insert earphones and/or sound field speakers. 
Applicable ANSI standards are: ANSI/ASA S3.6-2004; ANSI S3.1-1999 (R 2003). 
 
Pure tone threshold exploration will be completed using the adaptive Hughson & 
Westlake procedure (1944). 
 
Sound field calibration will be completed as recommended by Katz (2002). The sound 
level meter should be set to the “A scale” and “slow” settings.  The sound level meter 
will be placed in the center of sound booth, approximately 1m from the loud speaker 
face, at the height of which would represent the center of an average subjects head. 
The calibration noise (test specific, however preferably speech spectrum noise) will be 
administered through the audiometer output to the loud speaker within the sound 
booth. The sound level meter detects the audiometer output through the loud speaker.  
With the VU meter on the audiometer set to 0 while, the dial on the audiometer is 
adjusted until the sound level meter within the sound booth detects the desired output. 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
39 
37 Appendix B: Instructions for Masking 
 
1. Puretone threshold is established in the test ear. 
2. Masking noise is introduced to the non-test ear at the initial masking level (10dB above 
the established threshold in the non-test ear). Puretone threshold then is re-established. 
3. Level of the masking tone or noise is increased subsequently by 5 dB.  If there is a 
response to the tone in the presence of the noise, the level of the noise is increased by 5 
dB.  If there is no response to the tone in the presence of the noise, the level of the tone 
is increased by 5-dB steps until a response is obtained. 
4. A plateau has been reached when the level of the noise can be increased over a range 
of 15 to 20 dB without shifting the threshold of the tone.  This corresponds to a response 
to the tone at the same HL when the masker is increased in three to four consecutive 
levels. 
5. Masked puretone threshold corresponds to the HL of the tone at which a masking 
plateau has been established. 
 
 
 

Post Approval Study:  Extended Duration Monitoring of Subjects with the Cochlear Nucleus Hybrid L24 Cochlear Implant System _  
Version 4 
September 9, 2014  
 
 
 
 
40 
38 Appendix C: Hearing Aid Fitting Guidelines 
Step 1 Create Hearing Aid Program 
Method: 
1. Using the hearing aid software, create a hearing aid program using the recipients’ 
audiogram. 
Step 2 Obtain Real Ear Unaided Response 
Method: 
1. Calibrate the probe tube. 
2. Position the patient one meter in front of the speaker. 
3. Place the probe tube in the ear canal approximately 25 to 30 mm past the tragal notch. 
4. Select recorded speech at conversational level, 65 dBSPL.  
5. Ensure the cochlear implant sound processor is turned OFF.  
6. Using a prescriptive algorithm (e.g.,NAL-NL1 or NAL-RP), obtain REUR. 
Step 3 Obtain Real Ear Aided Response 
Method: 
1. With the probe tube in place, insert the hearing aid. Ensure that it is ON and detected by 
the hearing aid software. Ensure the cochlear implant sound processor is turned OFF.  
2. Select recorded speech at conversational level, 60 dBSPL.  
3. Allowing for subjective report, adjust hearing aid software to match real ear target gain 
and maximum output. 
Step 4 Balance hearing aid and cochlear implant loudness (if applicable) 
Method: 
1. With the hearing aid connected to the hearing aid software, turn the cochlear implant 
sound processor ON. 
2. Select recorded speech at conversational level, 60 dBSPL.  
3. Ask the patient to point to which side is loudest or if the sound is balanced. 
4. Use the conversational recorded speech to adjust the gain in the hearing aid software as 
needed to balance the loudness the between the two devices. 
5. Repeat for soft speech (50 dB SPL). 
6. Adjust the compression ratio and/or compression threshold in the hearing aid as needed 
so that soft speech is audible and equal in volume. 
7. Repeat for loud speech (85 dB SPL). 
8. Adjust the maximum power output of the hearing aid as needed so that loud sounds do 
not exceed the patient’s loudness discomfort level.