A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy of SPI-1005 in Meniere's Disease
Phase: PHASE2
Conditions: Meniere's Disease
Sponsor: Sound Pharmaceuticals, Incorporated

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
CLINICAL RESEARCH PROTOCOL 
DRUG: 
SPI‑1005 
STUDY NUMBER(S): 
SPI‑1005‑251 
PROTOCOL(S) TITLE: 
A PHASE 2b, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY TO 
EVALUATE THE SAFETY AND EFFICACY OF 
SPI-1005 IN MENIERE’S DISEASE 
IND NUMBER: 
127540 
SPONSOR: 
Sound Pharmaceuticals, Inc. 
4010 Stone Way N., Suite 220 
Seattle WA, 98103 
Phone: 206-634-2559 
FAX: 206-691-8262 
ORIGINAL PROTOCOL DATE: 
21 August 2017 
VERSION NUMBER: 
1.00 
VERSION DATE: 
21 August 2017 
CHEMICAL NAME:  2-phenyl-1,2-benzisoselenazol-3 (2H) -one 
Lead Investigator: 
Company Contact: 
Paul R Lambert, MD, FACS 
 
Jonathan Kil, MD 
Dept. of Otolaryngology-HNS.  
Sound Pharmaceuticals, Inc. 
135 Rutledge Ave 10th Floor 
 
4010 Stone Way North 
Medical University of South Carolina 
Suite 120  
Charleston, SC 29425  
Seattle, WA 98103 
NCT Number:  03325790 

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
1 PROTOCOL SUMMARY 
1.1 
Synopsis 
SPI-1005-251: CLINICAL TRIAL SYNOPSIS 
Title 
A PHASE 2b, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED STUDY TO EVALUATE THE SAFETY AND 
EFFICACY OF SPI-1005 IN MENIERE’S DISEASE  
Study 
Objective(s) 
The primary objective of this Phase 2 study is to determine the: 
•
Safety of SPI-1005 treatment in adults with Meniere’s disease.
•
Efficacy of SPI-1005 will be determined by the following
clinically significant methods and measures (responder
analysis):

Pure tone audiometry (>30 dBHL at 250, 500 or 1000 Hz)
>10 dB improvement from baseline
Words in Noise Test (0-35)
>10 % increase from baseline
Tinnitus Functional Index (TFI) (0-100)
>10 pt. reduction from baseline
Tinnitus Loudness: Q#2 of TFI (0-10)
>2 pt. reduction from baseline
Vertigo Symptom Scale (0-60)
>6 pt. reduction from baseline
The responder analysis from each method and measure will be 
compared between treatment groups for significance. 
•
Efficacy of SPI-1005 treatment in adults with Meniere’s
disease based on
o
Improvement in sensorineural hearing loss using pure
tone audiometry at 250, 500, or 1000 Hz; or
o
Word recognition score using WIN testing at 24, 20,
16, 12, 8, 4 and 0 SNR; or
o
Improvement in the Tinnitus Functional Index (TFI); or
o
Improvement in Tinnitus Loudness (TL); or
o
Improvement in the Vertigo Symptoms Scale (VSS).
The secondary objectives of this study are to determine the: 
•
Pharmacokinetics of SPI-1005.
Study Design 
Randomized Double Blind Placebo Controlled Study of SPI-1005 in 
adult volunteers with Meniere’s Disease (probable or definitive 

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
SPI-1005-251: CLINICAL TRIAL SYNOPSIS 
diagnosis) with active symptoms in the months preceding study 
enrollment. All subjects will undergo baseline audiometric testing and 
have their severity of sensorineural hearing loss, tinnitus and vertigo 
determined before initiating treatment. Subjects will be randomized to 
treatment, either placebo or two different doses of SPI-1005 (1:1:1) 
and treated for 28 days. Subjects will return to clinic 2 weeks after the 
start of study drug to have safety assessments and to receive additional 
study drug. Subjects will return to clinic at week 4 to have their 
hearing loss, tinnitus and vertigo re-assessed, and again 4 weeks after 
the end of study drug treatment. Therefore, 4 scheduled clinic visits 
will be performed over an 8 week period. Audiometry will be 
performed at baseline, at the end of the 4 week treatment period, and 4 
weeks after treatment has stopped. The TFI and VSS will be 
performed at all scheduled clinic visits. Subjects are allowed to 
continue with their existing maintenance therapies (i.e. low salt diet, 
thiazide diuretic, or other PRN medications) except for the use of oral 
or locally injected steroids. New treatments should be avoided while 
on study.  
Study Centers 
Approximately 12 U.S. sites will participate in this study 
Subjects 
120 male and female adults with probable or definitive Meniere’s 
disease.  
Inclusion 
Criteria 
•
Adult male and female patients, 18-75 years of age at the time
of enrollment.
•
Diagnosis of probable or definitive Meniere’s disease by AAO-
HNS 1995 criteria (Section 12.1, APPENDIX I).
•
Two of three active symptoms including vertigo or
disequilibrium, fluctuating hearing loss, or tinnitus within the 3
months prior to study enrollment.
•
Hearing loss of >30 dBHL at either 250, 500 or 1000 Hz.
•
Voluntary consent to participate in the study.
•
Male subjects that are willing to use condoms throughout the
study period and 90-days following study completion even if
not fertile.
•
Females of childbearing potential should either be sexually
inactive (abstinent) for 14 days prior to screening and
throughout the study or be using one of the following acceptable
birth control methods:
o
IUD in place for at least 3 months prior to study; or
o
Barrier method (condom or diaphragm) with spermicide
for at least 14 days prior to screening through study
completion; or
o
Stable hormonal contraceptive for at least 3 months prior

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
SPI-1005-251: CLINICAL TRIAL SYNOPSIS 
to study and through study completion; or 
o
Surgical sterilization (vasectomy) of partner at least 6
months prior to study enrollment.
•
Females of non-childbearing potential should be surgically
sterile (bilateral tubal ligation with surgery at least 6 months
prior to study enrollment, hysterectomy, or bilateral
oophorectomy at least 2 months prior to study) or be at least 1
year since last menses.
Exclusion 
Criteria 
•
Current use of or within 60 days prior to study IV ototoxic
medications such as chemotherapy including cisplatin,
carboplatinum, or oxaliplatin; aminoglycoside antibiotics
including gentamicin, amikacin, tobramycin, kanamycin, or
streptomycin; or loop diuretics including furosemide.
•
History of otosclerosis or vestibular schwannoma.
•
History of significant middle ear or inner ear surgery.
•
Current conductive hearing loss, otitis media, or mixed hearing loss.
•
Significant cardiovascular, pulmonary, hepatic, renal, hematologic,
gastrointestinal, endocrine, immunologic, or psychiatric disease.
•
Current use or within 30 days prior to study enrollment systemic
steroids or drugs known to be strong inhibitors or inducers of
cytochrome P450 enzymes.
•
Hypersensitivity or idiosyncratic reaction to compounds related to
ebselen or selenium.
•
Female patients who are pregnant or breastfeeding.
•
Participation in another interventional drug or device study within
30 days prior to study consent.
Study Duration Estimated duration of 12 months 
Participant 
Duration 
Participation for each study participants will be approximately 8 to 12 
weeks across 4 clinic visits. 
Dose & 
Regimen 
Subjects will receive either SPI-1005 or matching placebo for 28 days. 
Treatment will be taken orally BID. Doses include 200 mg or 400 mg 
of ebselen or matching placebo in capsule form. Two week supplies 
will be provided on Clinic Visit 1 and 2. 

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
SPI-1005-251: CLINICAL TRIAL SYNOPSIS 
Safety & 
Tolerability 
Assessments 
Physical examinations, vital signs, adverse events, hematology (CBC) 
and serum chemistries will encompass safety assessments. 
Adverse events will be coded using MedDRA (Version 18.1 or 
higher) and summarized by treatment group for the number of adverse 
events and compared. 
Vital signs and clinical laboratory results will be summarized for each 
treatment group and compared. 
PK 
Assessments 
The trough plasma levels of ebselen and its major metabolite (2-
glucuronyl selenobenzanilide) will be determined using LC-MS/MS. 
The corresponding selenium plasma levels will be determined by ICP-
MS. 
PK results will be summarized by treatment group. 
Lead 
Investigator (s) 
Paul R. Lambert, MD 

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
1.2 
Schema 
Screen for 
Eligibility 
Day -28 to 1 
Day 14 
Day 28 
Day 56 
Screen participants (n=168 estimate) by inclusion and exclusion criteria 
including history and review of systems 
Clinic Visit 1 
Informed consent process, perform baseline assessments, confirm 
eligibility, randomize, complete enrollment by providing study drug. 
Refer to Section 1.3, Schedule of Assessments 
Clinic Visit 3 
Perform protocol required assessments. 
Refer to Section 1.3, Schedule of Assessments 
Clinic Visit 4 
Final Assessments 
Refer to Section 1.3, Schedule 
of Assessments 
Clinic Visit 2 
Perform protocol required assessments. 
Refer to Section 1.3, Schedule of Assessments 
Estimated Excluded (n=48) 
• Did not meet I/E criteria (n=25)
• Declined to participate (n=13)
• Other reasons (n=10)

Sound Pharmaceuticals, Inc. 
IND 127540 
SPI-1005 
Submission 0003 
1.3 
Schedule of Assessments 
Clinic Visit 
CV1 
(Screening/Baseline) 
CV2 
CV3 
CV4 
Study Day 
-28 to 1 
14 (+/- 3) 
28 (+/- 3) 
56 (+/-3) 
Informed 
Consent 
X 
Demographics 
X 
Medical 
History 
X 
Physical Exam  
X 
X 
X 
X 
Hight 
X 
Weight 
X 
X 
X 
X 
BMI 
X 
Vital Signs 
X 
X 
X 
X 
CBC 
X 
X 
X 
X 
Serum 
Chemistry 
X 
X 
X 
X 
Urine 
Pregnancy (1) 
X 
Otoscopy 
X 
X 
X 
Tympanometry 
X 
TFI 
X 
X 
X 
X 
VSS 
X 
X 
X 
X 
PTA 
X 
X 
X 
WINT 
X 
X 
X 
Concomitant 
Medication 
Review  
X 
X 
X 
X 
Randomization 
X 
SPI-1005 
Treatment (2) 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
PK 
X 
X 
X 
X 
(1) Urine pregnancy test on CV1 screening visit only. 
(2) SPI-1005 treatment begins after safety labs (CBC, serum chemistry) are reviewed and all inclusion/exclusion
criteria are met.