A Multicenter, Randomized, Double-Blinded, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of 3 Concentrations of Topically Applied BBI-4000 (Sofpironium Bromide) Gel in Subjects With Axillary Hyperhidrosis
Phase: PHASE2
Conditions: Hyperhidrosis
Sponsor: Botanix Pharmaceuticals

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 1 of 65 
CONFIDENTIAL 
22 February 2017 
 
CONFIDENTIAL 
A Multicenter, Randomized, Double-Blinded, Vehicle-Controlled 
Study to Evaluate the Safety and Efficacy of 5%, 10% and 15% 
Topically Applied BBI-4000 (Sofpironium Bromide) Gel in Subjects 
with Axillary Hyperhidrosis 
PROTOCOL NUMBER:  
BBI-4000-CL-203 
NAME OF INVESTIGATIONAL PRODUCT: 
BBI-4000 (Sofpironium Bromide)  
ORIGINAL PROTOCOL: 
November 22, 2016 
AMENDMENT 1 
February 22, 2017 
SPONSOR: 
 
Brickell Biotech, Inc. 
5777 Central Ave., Suite 102 
Boulder, CO 
PHASE: 
2 
IND Number: 
121,256 
Medical Monitor: 
William J. Cunningham, MD 
Cu-Tech, LLC 
333 US Highway 46W 
Mountain Lakes, NJ 07046 
Phone: 973-331-1620 
Fax: 973-331-1622 
Email: wcunningham@cu-tech.com   
 
Copyright 2016 Brickell Biotech, Inc.  All rights reserved.  Unauthorized copying or use of this 
information is prohibited. 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 2 of 65 
CONFIDENTIAL 
22 February 2017 
SPONSOR SIGNATORY: 
 
 
 
 
 
Patricia Walker, MD, PhD 
President and Chief Scientific Officer 
 
Date 
 
2/23/2017

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 3 of 65 
CONFIDENTIAL 
22 February 2017 
INVESTIGATOR SIGNATURE PAGE 
I agree to: 
 
x Implement and conduct this study diligently and in strict compliance with the protocol, 
good clinical practices (GCPs), and all applicable laws and regulations. 
 
x Maintain all information supplied by Brickell Biotech, Inc. in confidence and, when this 
information is submitted to an Institutional Review Board (IRB) or another group, it will be 
submitted with a designation that the material is confidential. 
 
 
I have read this protocol in its entirety and I agree to all aspects. 
 
 
 
 
___________________________________________________________________________ 
Investigator Printed Name  
 
 
Signature  
 
 
Date 
 
 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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22 February 2017 
TABLE OF CONTENTS 
SPONSOR SIGNATORY: .............................................................................................................. 2 
INVESTIGATOR SIGNATURE PAGE........................................................................................ 3 
TABLE OF CONTENTS ................................................................................................................ 4 
SYNOPSIS ........................................................................................................................................ 8 
ABBREVIATIONS ........................................................................................................................ 11 
1 BACKGROUND AND CLINICAL RATIONALE .............................................................. 13 
2 STUDY DESIGN ...................................................................................................................... 20 
3 STUDY OBJECTIVES AND ASSESSMENTS .................................................................... 21 
3.1 
Study Objectives .................................................................................................................. 21 
3.2 
Study Assessments ............................................................................................................... 21 
4 STUDY POPULATION .......................................................................................................... 22 
4.1 
Number of Subjects ............................................................................................................. 22 
4.2 
Inclusion Criteria ................................................................................................................ 22 
4.3 
Exclusion Criteria ............................................................................................................... 23 
5 INVESTIGATIONAL PRODUCT (IP) ................................................................................. 25 
5.1 
Methods for Masking/Blinding .......................................................................................... 25 
5.2 
Storage of Investigational Product .................................................................................... 26 
5.3 
Instructions for Use and Administration of Investigational Product ............................. 26 
5.4 
Instructions for the Subjects .............................................................................................. 27 
6 CONCOMITANT MEDICATIONS/TREATMENTS ......................................................... 28 
6.1 
Permissible Medications/Treatments ................................................................................ 28 
6.2 
Prohibited Medications/Treatments .................................................................................. 28 
7 PROCEDURES ........................................................................................................................ 29 
7.1 
Time and Events Table ....................................................................................................... 30 
7.2 
Visit-Specific Procedures .................................................................................................... 31 
7.2.1 
Visit 1 (Screening) .......................................................................................................... 31 
7.2.2 
Visit 2 (GSP1) and Visit 3 (GSP2) – during Screening period ................................... 32 
7.2.3 
Visit 4 (Rescreening, GSP3) – during Screening period. ............................................ 32 
7.2.4 
Visit 5 (Baseline, within 2-7 Days after Rescreening/Visit 4) ..................................... 32 
7.2.5 
Visit 6 (Day 8 ±2) and Visit 7 (Day 15 ±2) .................................................................... 33 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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7.2.6 
Visit 8 (Day 22 ±2) .......................................................................................................... 33 
7.2.7 
Visit 9 (Day 29 ±2) .......................................................................................................... 34 
7.2.8 
Visit 10 (Day 36 ±2) ........................................................................................................ 35 
7.2.9 
Visit 11 (Day 41 ±2, GSP4) and Visit 12 (Day 42 ±2, GSP5) ...................................... 35 
7.2.10 
Visit 13 (Day 43 ±2, GSP6) / End of Treatment ........................................................... 35 
7.2.11 
Visit 14 (Day 57 ±3) / 2 Week Follow-up / End of Study ............................................ 36 
7.3 
Unscheduled Visits .............................................................................................................. 36 
7.4 
Early Discontinuation of Subjects ..................................................................................... 36 
8 RESPONSE MEASURES AND SUMMARY OF DATA COLLECTION METHODS ... 37 
8.1 
Efficacy Measures ............................................................................................................... 37 
8.2 
Safety Measures ................................................................................................................... 37 
8.2.1 
Physical Exam ................................................................................................................. 37 
8.2.2 
Vital Signs ....................................................................................................................... 38 
8.2.3 
Clinical Laboratory Assessments .................................................................................. 38 
8.2.4 
Adverse Events ............................................................................................................... 38 
8.2.5 
Subject Assessments ....................................................................................................... 39 
8.2.6 
Local Tolerability Assessments ..................................................................................... 39 
8.3 
Summary of Methods of Data Collection .......................................................................... 39 
9 ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) ......................... 40 
9.1 
Safety Assessments .............................................................................................................. 40 
9.1.1 
Method of Detecting AEs and SAEs ............................................................................. 40 
9.2 
Reporting Requirements .................................................................................................... 41 
9.2.1 
Serious and/or Unexpected Adverse Events ................................................................ 41 
9.2.2 
Adverse Event Reporting ............................................................................................... 41 
9.2.3 
Pregnancy ........................................................................................................................ 42 
9.2.4 
Follow-up and Final Reports ......................................................................................... 43 
9.3 
Procedures for Unblinding of Investigational Product.................................................... 44 
10 STATISTICAL PROCEDURES ............................................................................................ 44 
10.1 Analysis Populations ........................................................................................................... 44 
10.2 Endpoints ............................................................................................................................. 45 
10.3 Efficacy Analyses ................................................................................................................. 46 
10.4 Safety Analyses .................................................................................................................... 47 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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10.5 Sample Size and Power Estimation ................................................................................... 47 
11 STUDY ADMINISTRATION PROCEDURES .................................................................... 48 
11.1 Subject Entry Procedures................................................................................................... 48 
11.1.1 
Overview of Entry Procedures ...................................................................................... 48 
11.1.2 
Informed Consent and Subject Privacy ....................................................................... 48 
11.1.3 
Method for Assignment to Study Product Groups ..................................................... 48 
11.2 Compliance with Protocol .................................................................................................. 49 
11.3 Study Termination .............................................................................................................. 49 
12 ADMINISTRATIVE ISSUES ................................................................................................. 50 
12.1 Posting of Information on Clinicaltrials.gov .................................................................... 50 
12.2 Protection of Human Subjects ........................................................................................... 50 
12.2.1 
Compliance with Informed Consent Regulations (US 21 CFR Part 50) and 
Relevant Country Regulations ...................................................................................... 50 
12.2.2 
Compliance with IRB Regulations ................................................................................ 50 
12.2.3 
Compliance with Good Clinical Practice ..................................................................... 50 
12.3 Changes to the Protocol ...................................................................................................... 50 
12.4 Subject Confidentiality ....................................................................................................... 50 
12.4.1 
Subject Privacy ............................................................................................................... 51 
12.5 Documentation .................................................................................................................... 51 
12.5.1 
Source Documents .......................................................................................................... 51 
12.5.2 
Electronic Case Report Form Completion ................................................................... 51 
12.5.3 
Retention of Documentation .......................................................................................... 51 
12.6 Labelling, Packaging, Storage, and Return or Disposal of Investigational Product .... 51 
12.6.1 
Labeling/Packaging ........................................................................................................ 51 
12.6.2 
Storage of Investigational Product ............................................................................... 52 
12.6.3 
Clinical Supply Inventory .............................................................................................. 52 
12.6.4 
Return or Disposal of Investigational Product ............................................................ 52 
12.7 Monitoring by the Sponsor ................................................................................................. 52 
12.8 Publications .......................................................................................................................... 52 
13 REFERENCES ......................................................................................................................... 53 
14 APPENDICES .......................................................................................................................... 54 
APPENDIX 1:  GRAVIMETRICALLY MEASURED SWEAT PRODUCTION .................. 54 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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APPENDIX 2:  HYPERHIDROSIS DISEASE SEVERITY SCALE (HDSS) ......................... 55 
APPENDIX 3:  HYPERHIDROSIS DISEASE SEVERITY MEASURE-AXILLA 
(HDSM-AX) .............................................................................................................................. 56 
APPENDIX 4:  QUALITY OF LIFE ASSESSMENT ............................................................... 59 
APPENDIX 5:  TOLERABILITY ASSESSMENTS .................................................................. 62 
APPENDIX 6:  STUDY DRUG APPLICATION & SUBJECT INSTRUCTIONS ................ 63 
APPENDIX 7:  EXAMPLE POTENT INHIBITORS OF CYP3A AND CYP2D6 ................. 65 
 
 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 8 of 65 
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22 February 2017 
SYNOPSIS 
STUDY TITLE:  A Multicenter, Randomized, Double-Blinded, Vehicle-Controlled Study to 
Evaluate the Safety and the Efficacy of 5%, 10% and 15% Topically Applied BBI-4000 
(Sofpironium Bromide) Gel in Subjects with Axillary Hyperhidrosis 
CLINICAL PHASE: Phase 2 (Confirmatory Study) 
STUDY OBJECTIVES:   
Primary: 
1. To evaluate the effect of BBI-4000 5%, 10% and 15 % gel on hyperhidrosis disease severity 
measure when applied topically in subjects with axillary hyperhidrosis. 
2. To evaluate the safety and local tolerability of BBI-4000 5%, 10% and 15% gel when applied 
topically in subjects with axillary hyperhidrosis. 
Secondary: 
1. To evaluate the effect of BBI-4000 5%, 10% and 15% gel on hyperhidrosis disease severity as 
it relates to sweat production, patient reported and quality of life self-assessments.  
 
STUDY ASSESSMENTS: 
 
Efficacy Assessments: 
The following assessment measures will be conducted to evaluate the efficacy of BBI-4000 5%, 
10% and 15% gel: 
x Hyperhidrosis Disease Severity Measurement-Axillary (HDSM-Ax) as measured by the 
subject 
x Gravimetrically measured sweat production (GSP) as measured by the investigator 
x Hyperhidrosis Disease Severity Scale (HDSS) as measured by the subject 
x Dermatology Life Quality Index (DLQI) as measured by the subject 
 
Safety Measures: 
The following safety assessment measures will be conducted: 
x Adverse events  
x Local tolerability assessments including burning, itching, dryness, scaling and erythema.  
x Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) 
x Laboratory tests (hematology, chemistry, and urinalysis) and pregnancy testing in females 
of child-bearing potential 
 
STUDY RATIONALE:   
This is a Phase 2 confirmatory, multicenter, randomized, double-blind, vehicle-controlled, parallel-
group study comparing a new formulation of BBI-4000 5%, 10% and 15% gel with vehicle 
(placebo) in subjects with axillary hyperhidrosis.  
Minor modifications to the BBI-4000 Topical Gel formulation have been made to replace the 
novel excipient, Dimethiconol Blend 20 (DB20), with isopropyl myristate (IPM). IPM is a well-

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 9 of 65 
CONFIDENTIAL 
22 February 2017 
characterized, compendial excipient commonly used in topical formulations; it is fully soluble in 
the formulation and thus overcomes the manufacturing issues previously encountered with DB20.  
Previous studies were conducted with the original formulation (i.e. DB20).  This study will be 
conducted with the new (to-be-marketed) formulation containing isopropyl myristate at 2.5% 
(w/w).  All other materials are common to both formulations and at the same concentrations. 
The BBI-4000 5%, 10% and 15% gel concentrations proposed for this Phase 2 study are expected 
to be safe and tolerable dose levels considering: 
x the safety and tolerability profile observed in the Phase 1 clinical study (BBI-4000-CL-01) 
with concentrations of BBI-4000 5%, 10% and 15% 
x the safety and tolerability profile observed in the Phase 1 clinical study (BBI-4000-CL-
101) with concentrations of BBI-4000 up to 10% 
x the PK, safety and tolerability profile observed in the Phase 2 study (BBI-4000-CL-201) 
with doses of 5%, 10% and 15% of BBI-4000 
x the safety and tolerability profile observed in the Phase 2 study (BBI-4000-CL-202) with 
doses of 15% of BBI-4000 
x the PK, safety and tolerability profile observed in the Phase 1 study (BBI-4000-CL-103) 
with doses of 5% and 15% of BBI-4000 
x tolerability observed in the minipig studies including concentrations up to 20% 
The estimated maximum drug exposure for the subjects enrolled in this Phase 2 study will be 
approximately 2.5 mg/kg/day (i.e., 1.3 mL of 15% BBI-4000 gel/day in a 70-kg adult). 
 
RISKS TO SUBJECTS: 
As an anticholinergic drug, topical administration of BBI-4000 gel could be associated with local 
reactions such irritation, erythema, burning, desquamation (scaling), and itch; as well as signs or 
symptoms typical of a systemic anticholinergic effect such as dry mouth, pupil dilation, blurred 
vision, dizziness, constipation, urinary retention, increase in body temperature, tachycardia, among 
others.  The previous BBI-4000 exposure to humans has demonstrated a low incidence of these 
effects which were mild in severity.  One subject who received BBI-4000 15% gel applied to the 
axillae in the Phase 2b (Study BBI-4000-CL-201) and two subjects who received BBI-4000 5 % 
and 15% gel applied to the axillae in the Phase 1 (Study BBI-4000-CL-103) study withdrew from 
the study due to anticholinergic AEs; moderate blurred vision, headache, urinary hesitation, and 
application site dryness (BBI-4000 15% CL-201 study); moderate urinary retention, mild dry eyes 
and dry mouth (BBI-4000 5% CL-103 study); and mild lightheaded and nausea (BBI-4000 15% 
CL-103 study). 
 
STUDY DESIGN:   
A maximum of 220 subjects, at approximately 25 clinical sites, will be enrolled to obtain 
approximately 200 subjects that have completed dosing and critical assessments. 
Subjects will be randomized to receive BBI-4000 5%, or 10%, or 15% gel, or vehicle gel (placebo) 
in a balanced ratio of 1:1:1:1.  

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 10 of 65 
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22 February 2017 
Subjects will apply the investigational product (BBI-4000 5% or 10% or 15% gel or vehicle gel); 
once daily at bedtime, to both axilla for 42 consecutive days. 
Gravimetric assessments and patient-reported outcomes HDSM-Ax, HDSS and DLQI will be 
recorded during the study at predefined time points. Vital signs, local tolerability assessments 
(including burning, itching, dryness, scaling and erythema assessed using standardized scales), and 
adverse events will be collected at each visit. A urine pregnancy test (UPT) for females of child-
bearing potential and blood and urine samples will be collected and analyzed at the Screening Visit 
and at the End of Treatment Visit for routine hematology, chemistry, and urinalysis parameters. 
A total of 14 scheduled visits will take place over approximately 12 to 16 weeks, depending on 
when the Baseline Visit (treatment) is scheduled after the four (4) screening period visits:  initial 
screening, GSP1 and GSP2, and Rescreening GSP3.  
 
INVESTIGATIONAL PRODUCT INFORMATION:   
BBI-4000 (sofpironium bromide) Gel is a clear to slightly translucent colorless gel packaged in a 
white colored, capped, metered pump container.  Two pumps are combined with 4 applicators to 
provide one kit to facilitate 42 days of dosing.  The total gel volume in each pump container is 45 
mL (~ 40 g).  The gross weight of each full pump container dispensed at Baseline and Visit 8 (Day 
22) is 74 to 80 grams. 
BBI-4000 (sofpironium bromide) 5%, 10%, or 15% Gel is an anhydrous gel formulation 
containing the drug substance in an anhydrous gel base comprising hydroxylpropyl cellulose NF, 
hexylene glycol NF, isopropyl myristate NF, citric acid anhydrous USP, and alcohol dehydrated 
USP.   
As previously noted, the drug product is provided in a kit containing two plastic metered pump 
containers each containing 45 mL of investigational product.  Each drug pump container is 
sufficient for 21 days of dosing, as dispensed per protocol instructions.  One pump actuation 
delivers ~ 0.67 mL of the gel formulation. 
BBI-4000 vehicle (placebo) gel will be identical in appearance and constituents to BBI-4000 
(sofpironium bromide) Gel but will not contain BBI-4000.  The placebo formulation is provided in 
the same plastic metered pump containers with the same applicators to provide matching kits.  The 
vehicle pump container contains 45 mL placebo product.  Each vehicle pump container is 
sufficient for 21 days of dosing, as dispensed per protocol instructions.  One pump actuation 
delivers ~ 0.67 mL of the placebo formulation. 
 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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22 February 2017 
ABBREVIATIONS 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
AUClast 
Area Under the Curve last measurement 
BBI 
Brickell Biotech, Inc. 
BPH 
Benign Prostatic Hyperplasia 
bpm 
Beats per minute 
C 
Celsius 
Cmax 
Maximum plasma concentration 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DB20 
Dimethiconol Blend 20 
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
FOCBP 
Female of Childbearing Potential 
g 
Grams 
GCP 
Good clinical practice 
GSP 
Gravimetric Sweat Production 
HDSS 
Hyperhidrosis Disease Severity Scale 
HDSM-Ax 
Hyperhidrosis Disease Severity Measure-Axillary 
HIPAA 
Health Insurance Portability and Accountability Act 
hr 
Hour 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
I/E 
Inclusion and Exclusion Criteria 
IND 
Investigational New Drug 
IP 
Investigational Product 
IPM 
Isopropyl Myristate 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IUD 
Intrauterine Device 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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22 February 2017 
IV 
Intravenous  
kg 
Kilogram 
L 
Left 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
min 
Minute 
mL 
Milliliter 
mm 
Millimeter 
mmHg 
Millimeter of mercury 
MMRM 
Mixed Model Repeated Measures 
NF 
National formulary 
ng 
Nanogram 
nM 
Nanomolar 
NOAEL 
No observed adverse effect level 
PK 
Pharmacokinetics 
PP 
Per-Protocol 
PRO 
Patient Reported Outcome 
PT 
Preferred term 
R 
Right 
SAE 
Serious Adverse Event 
SC 
Subcutaneous 
SOC 
System organ class 
SSRI 
Selective serotonin re-uptake inhibitors 
Tmax 
Time of maximum plasma concentration 
US 
United States of America 
UPT 
Urine Pregnancy Test 
USP 
United States Pharmacopeia 
 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 13 of 65 
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22 February 2017 
1 
BACKGROUND AND CLINICAL RATIONALE 
BBI-4000 (sofpironium bromide) is a novel soft-anticholinergic ester analog of glycopyrrolate in 
development for the topical treatment of hyperhidrosis. BBI-4000 is a competitive inhibitor of 
acetylcholine receptors that are located on certain peripheral tissues, including sweat glands. BBI-
4000 gel is expected to inhibit the action of acetylcholine in sweat glands thereby reducing the 
extent of sweating. Please refer to the BBI-4000 Investigator’s Brochure for more information on 
BBI-4000. 
Hyperhidrosis is a disorder of excessive sweating beyond what is expected for thermoregulatory 
needs and environmental conditions. Primary hyperhidrosis (armpits, hands, and feet) affects 
approximately 4.8% of the population in the US (Doolittle, 20161) and is believed to be caused by 
an overactive cholinergic response of the sweat glands. Current therapies have limitation in their 
efficacy, significant side effects, and/or are invasive and costly.  
Oral and topical anticholinergic drugs, such as glycopyrrolate, have been used to treat 
hyperhidrosis, although they are not currently approved for this indication in the US. Their main 
limitation is the systemic anticholinergic side effects (blurred vision, dizziness, dry mouth, 
constipation, urinary retention, and tachycardia). 
“Soft-drugs” are designed to provide maximal therapeutic effect with minimal side effects. The 
synthesis of a “soft-drug” is achieved by starting with a known inactive or minimally active 
metabolite of a known active drug (e.g., glycopyrrolate); the inactive metabolite is then structurally 
modified to an active form that will undergo a predictable one-step transformation back to the 
inactive or less active metabolite in vivo. Thus, the “soft-drug” concept is based upon predictable 
metabolic deactivation processes by hydrolysis and enzymes found predominately in the systemic 
circulation.  
Based on these concepts, BBI-4000 was designed as a structural analog of glycopyrrolate, a well-
known potent anticholinergic. The ester structure of BBI-4000 allows for a rapid conversion via 
enzymatic and hydrolytic processes into a noticeably less active metabolite (carboxylic acid 
metabolite, referred to as BBI-4010). The predicted metabolite (BBI-4010) is highly polar and 
ionized at physiological pH and thus should be subject to rapid elimination from the systemic 
circulation. This drug design is expected to result in a reduction of the potential undesirable 
systemic anticholinergic effects while maintaining the intended topical anticholinergic effect. 
In this bridging study, we are studying a new formulation of the BBI-4000 gel product against 
vehicle gel (placebo) group.  The previously studied formulation included 2.5% of Dimethiconol 
Blend (DB20) as an excipient.  Minor modifications to the BBI-4000 (Sofpironium Bromide) Gel 
formulation have been made to replace DB20 with isopropyl myristate (IPM).  DB20 was included 
in the original formulation at a low concentration (i.e. 2.5% w/w) to reduce the tackiness of the 
formulation during drying after application.  During process scale up, DB20 could not be 
physically stabilized in the formulation, so an alternative excipient was identified.  IPM is a well-
characterized, compendial excipient commonly used in topical formulations; it is fully soluble in 
the formulation and thus overcomes the manufacturing issues previously encountered with DB20. 
All other materials are common to both formulations at the same concentrations. 
The drug product is an anhydrous, clear to slightly translucent colorless gel with the following 
constituents: BBI-4000 as active ingredient, hydroxypropyl cellulose as a gelling agent, hexylene 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 14 of 65 
CONFIDENTIAL 
22 February 2017 
glycol as a humectant, isopropyl myristate to increase the aesthetic properties of the gel (i.e. skin 
conditioner/lubricant), citric acid for pH adjustment and ethanol as the anhydrous vehicle.  
The in-vitro penetration and permeation data indicate that the IPM formulation should provide 
similar deposition and exposure of topically applied BBI-4000 as compared to the original 
formulation containing DB20. In nonclinical repeat-dose bridging studies in mice and minipigs, 
the BBI-4000 IPM gel containing IPM exhibited a comparable toxicity profile to that of the 
original formulation.    Hence, the change in formulation is not anticipated to result in increased 
risk to subjects participating in this study. 
Nonclinical investigations showed that BBI-4000 is able to induce dose-dependent pupil dilation 
when applied to rabbit eyes, demonstrating its local anticholinergic effect.  The maximum 
mydriatic effect is comparable to glycopyrrolate but with a shorter duration, as expected by its 
structural design. In this model, glycopyrrolate maintains pupil dilation for an extended period 
(i.e., ≈ 50% of maximum mydriasis remained at Day 3 following a single instillation of 0.2% 
solution), indicative of its long-lasting anticholinergic effect. The effect of BBI-4000, although of 
shorter duration (i.e., ≈ 50% of maximum mydriasis remained at 24 hours post instillation of 1% 
solution), demonstrates sufficient local anticholinergic effect while minimizing the potential risk of 
long-lasting side effects.  
Systemic administration of BBI-4000 did not adversely affect the central nervous system in a 
functional observational assessment in rats or in a respiratory function evaluation in dogs. As 
expected by virtue of its mechanism of action as an anticholinergic drug, intravenous (IV) bolus 
infusion of BBI-4000 in dogs resulted in temporary increases in heart rate.  
BBI-4000 is extensively metabolized in human hepatocytes, and in animal and human liver 
microsomes.  The primary metabolite, BBI-4010, is formed by ester hydrolysis.  Additional 
metabolism studies, and excretion studies, are ongoing.  The in vitro plasma protein binding of 
BBI-4000 and BBI-4010 is low and independent of concentration. 
The dermal and systemic toxicity of BBI-4000 gel was also investigated in a battery of 
nonclinical studies in rats, minipigs, dogs, and guinea pigs.  
Repeat-dose toxicity studies of BBI-4000 DB20 gel were conducted in mice for durations of up to 
13-weeks.  Daily dermal unoccluded administration of up to 20% BBI-4000 DB20 gel for 23 h/day 
at a maximum target dose of 400 mg/kg/day was well tolerated without systemic toxicity.  There 
were no BBI-4000-related dermal observations, adverse effects on body weight, food 
consumption, hematology parameters or organ weights. Toxicokinetics showed high inter-
individual variation in plasma BBI-4000 concentrations in both genders thus establishment of a 
clear dose-response relationship and accumulation with repeat-dosing were not feasible.  Overall, 
systemic BBI-4000 Cmax and AUC24 did consistently increase with increasing dose and females 
generally exhibited higher systemic exposure than males.  BBI-4010 exposures were also highly 
variable, plasma increases were non-dose-proportional, females had lower BBI-4010 exposure 
than males, and there was evidence of accumulation.  A NOAEL was not established due to the 
non-dose-related, and pharmacologically mediated, mortality. 
In minipigs, daily repeat-dose dermal administration of up to 20% BBI-4000 DB20 gel at a 
maximum dose of 76 mg/kg/day has been evaluated for up to 26-weeks (a 39-week toxicity study 
is on-going).  No mortality or systemic toxicity has been observed in any study.  Unoccluded 
dermal dosing for 23 h/day was well tolerated without BBI-4000-related effects on clinical signs, 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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CONFIDENTIAL 
22 February 2017 
physical examination, food consumption, body weights, clinical pathology, ophthalmology, ECG 
waveforms or intervals, organ weights, macroscopic examination or histology.  Dermal 
observations of minimal irritation at the dosing sites have been observed.  In the completed 28-day 
study, a NOAEL for BBI-4000 DB20 gel was considered to be >76 mg/kg/day (20% gel to ~10% 
BSA) corresponding to Day 28 AUC values of 3.80 ng•hr/mL and 7.93 ng•hr/mL in males and 
females, respectively.  Toxicokinetic evaluation is on-going in the 39-week study.   
BBI-4000 was administered subcutaneously (SC) to rats for up to 26-weeks.  This SC route was 
chosen following completion of a 2-week dermal PK study of BBI-4000 DB20 gel in rats in which 
dermal tolerance was shown to be limited.  The incidence and severity of dose-related erythema 
desquamation, and eschar was considered to preclude long-term repeat dosing by the topical route 
in rats. 
SC doses of 20 mg/kg/day and 10 mg/kg/day BBI-4000 were evaluated in 7-day, and 28-day 
studies, respectively.  There was no mortality or systemic toxicity; a Maximal Tolerated Dose 
(MTD) of 5 mg/kg/day BBI-4000 (in 0.9% NaCl) was determined for extended repeat dosing 
based on local injection site reactions.  In pivotal studies, non-dose-related pharmacologically 
mediated mortality occurred due to ingestion of bedding material and food which lodged in the 
pharynx.  Clinical signs included retching, gasping, piloerection, somnolence and anticholinergic-
related mydriasis.  There were no consistent signs of injection site irritation.  Dose-related 
decreases in body weight/body weight gain and slight decreases in food consumption were noted 
in both genders.  Systemic BBI-4000 and BBI-4010 exposures, based on AUC24, increased with 
increasing dose over the dose range of 0.5 to 5.0 mg/kg/day, and increases were generally greater 
than dose-proportional. Both analytes showed evidence of accumulation over 13-weeks and 26-
weeks of repeat daily dosing.  Based on the results of the SC injection studies, a NOAEL of 
0.5 mg/kg/day, and an MTD of 5 mg/kg/day, were identified for SC administration to rats. 
The reformulated BBI-4000 IPM gel was evaluated in bridging toxicity studies in mice and 
minipigs. No toxicologically significant differences were noted between formulations in either 
species.  In mice, there was no mortality or systemic toxicity associated with 15-days of 
unoccluded 23 h/day exposures to BBI-4000 IPM gel.  No dermal signs, drug-related clinical 
observations, effects on body weight, or toxicologically significant effects on food consumption 
were observed. As was observed with BBI-4000 DB20 gel, systemic exposure to BBI-4000 and 
BBI-4010 was highly variable.  Systemic BBI-4000 Cmax and AUC23 did not show a consistent 
increase with increasing dose over the target dose range 100 to 400 mg/kg/day (density corrected 
doses of 84, 171 and 354 mg/kg/day BBI-4000).  BBI-4010 plasma exposure was also highly 
variable but increased approximately proportionally to dose.  There was no obvious gender 
difference; accumulation was not determined. A NOAEL of 400 mg/kg/day BBI-4000 (20% IPM 
gel concentration) was established for both genders. 
In minipigs, the reformulated 20% BBI-4000 IPM gel was compared to 20% BBI-4000 DB20 gel 
at 23 h/day unoccluded dose of 76 mg/kg/day for 28 consecutive days.  There was no systemic 
toxicity, clinical observations, or adverse effects on body weights, food consumption or clinical 
pathology in BBI-4000 or vehicle treated minipigs for either formulation.  Dermal irritation was 
limited to intermittent slight focal erythema which was similar between formulations and vehicles.  
Toxicokinetic evaluation showed that plasma BBI-4000 concentrations were variable in both dose 
groups; by Day 28, the mean combined gender AUC0-last of BBI-4000 was 2.8-fold higher, and 
Cmax was approximately 4-fold higher, after topical application of the IPM formulation than after 

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exposure to the DB20 gel formulation. BBI-4010 AUC0-last and Cmax were approximately 2.0-fold 
higher in the IPM group than the DB20 group.  
BBI-4000 did not demonstrate sensitization potential in guinea pigs.  Additionally, BBI-4000 gel 
does not absorb UV in the photoactivation range and is thus not a direct photochemical 
photosensitizer.  BBI-4000 gel did show a potential to cause eye damage in vitro.   
Results from in vitro and in vivo genotoxicity studies did not identify a mutagenic or clastogenic 
risk for BBI-4000.  A dermal carcinogenicity study in mice evaluating BBI-4000 gel, and a 
carcinogenicity evaluation of subcutaneous BBI-4000 in rats are planned to start before the end of 
2016. 
Overall, Brickell has completed a comprehensive panel of nonclinical studies to characterize the 
toxicity and safety profile of BBI-4000, including in vitro and in vivo pharmacology studies 
(nonclinical efficacy); cardiovascular, respiratory and central nervous system safety pharmacology 
studies; absorption, protein binding, metabolism, and TK studies; repeat-dose toxicity, 
reproductive and genetic toxicity; sensitization and ocular irritation studies; and drug product 
formulation bridging toxicity studies.  A 39-week chronic repeat-dose dermal toxicity study in 
minipigs is currently in progress (week 26 is complete).  Additional pharmacology; absorption, 
distribution, metabolism, excretion and drug-drug interaction studies; and reproductive toxicity 
studies are on-going or are planned.  Systemic and dermal carcinogenicity studies are under 
initiation 
Prior Human Experience 
As of 1 October 2016, 5 clinical studies have been conducted with BBI-4000 gel exposing 244 
subjects to the active ingredient: two Phase 1 studies in healthy adults, Phase 1 and Phase 2 studies 
in adults with primary axillary hyperhidrosis, and a Phase 2 study in adults with primary palmar 
hyperhidrosis.  
To date, the majority of the clinical program was conducted with a gel formulation consisting of 
BBI-4000 dissolved in an anhydrous base of hydroxypropyl cellulose, hexylene glycol, citric acid 
anhydrous, dehydrated alcohol, and the novel excipient Dimethiconol Blend 20 (DB20), used to 
improve the gel product's aesthetic properties. To address DB20 physical stability concerns during 
scale up, a reformulated gel was created that substitutes DB20 with isopropyl myristate (IPM, a 
common compendial excipient). The two gel formulations are quantitatively the same, with DB20 
being replaced with IPM at the same concentration resulting with a gel of similar density. In 
nonclinical repeat dose bridging studies in mice and minipigs, the BBI 4000 IPM gel exhibited a 
comparable toxicity profile to that of the original DB20 formulation. The IPM gel was first 
clinically introduced in study BBI-4000-CL-103 (see below). 
Study BBI-4000-01 (ex-US)  
This was a Phase 1, randomized, within-group controlled, double-blind study of BBI-4000 DB20 
gel conducted in 28 healthy adult males. The objective of this study was to investigate skin 
irritability and safety of a single application of BBI-4000 gel by patch test. Each subject received 
all of the following substances applied on the back, which were left on the subjects for 48 hours: 
5%, 10%, and 15% BBI-4000 DB20 gel; 0% BBI-4000 DB20 gel (placebo); 0.5% sodium lauryl 
sulfate solution (positive-control); deionized water (negative-control); and patch test unit only. 
All subjects completed the study. Only a few subjects expressed weak skin reactions (International 

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Contact Dermatitis Research Group [ICDRG] grade 1) after application of BBI-4000 gel in a patch 
test, which were not judged as adverse events (AEs) by investigators. Further, BBI-4000 gel induced 
skin reactions compatible to those seen with purified water, the negative control. Dose-related 
reactions to BBI-4000 were not identified, and no systemic AEs were reported in subjects.  
 
Study BBI-4000-CL-101  
This was a Phase 1, randomized, double-blind, single-center study conducted in 24 subjects with 
primary axillary hyperhidrosis. The objective of this study was to investigate the local tolerability, 
safety, and effect of BBI-4000 DB20 gel on sweat production (using gravimetric and 
Hyperhidrosis Disease Severity Scale [HDSS] methods). The study consisted of 2 consecutive 
cohorts, where Cohort 1 (N = 6) established acceptable tolerability of 5% BBI-4000 DB20 gel 
(applied to one axilla) and vehicle gel to the other axilla prior to enrolling a separate group of 
subjects into Cohort 2. Subjects in Cohort 2 (N = 18; 6 in each group) were randomized to receive 
5% BBI-4000 DB20 gel, 10% BBI-4000 DB20 gel, or vehicle gel (control) to both axillae once 
daily for 14 days.  
All 24 subjects completed the study. Local tolerability assessments indicated that 5% and 10% 
BBI-4000 DB20 gel topically applied to the axilla region was well tolerated over the 14-day 
treatment period. Minimal to mild erythema, itching, burning, and dryness were reported during 
treatment, usually limited to only 1 study visit and resolved spontaneously. No AEs, SAEs or 
deaths were reported.  
The primary endpoint of mean percent reduction from baseline in sweat production at Day 15 was 
63.2% and 67.6% for subjects treated with 5% and 10% BBI-4000 DB20 gel, respectively 
(compared to 52.4% subjects treated with vehicle gel). Overall, the subjects receiving BBI-4000 
experienced better efficacy outcomes. Specifically, 67% of subjects receiving BBI-4000 DB20 gel 
(5% and 10% groups combined) achieved a ≥ 2-point improvement in the HDSS in comparison to 
33% of subjects who received vehicle; and 75% of subjects receiving BBI-4000 (5% and 10% 
groups combined) achieved ≥ 50% sweat reduction compared to 33% of subjects who received 
vehicle. While BBI-4000 10% appeared to have a greater effect than BBI-4000 5% DB20 gel with 
regard to several efficacy outcomes, a larger study was required to confirm this potential 
difference.  
Study BBI-4000-CL-201  
This was a Phase 2, multicenter, randomized, double-blind, vehicle-controlled, parallel group 
comparison study of 3 concentrations of BBI-4000 DB20 gel (i.e. 5%, 10%, and 15%) in 189 
adults with primary axillary hyperhidrosis. The objectives of this study were to evaluate the safety 
and local tolerability of BBI-4000 DB20 gel; the effect of BBI-4000 DB20 gel as assessed by the 
HDSS and sweat production; the PK of BBI-4000; the effect of BBI-4000 gel as assessed by the 
Hyperhidrosis Disease Severity Measure-Axillary Scale (HDSM-Ax); and the psychometric 
performance of the HDSM-Ax as a measure of hyperhidrosis severity.  
Subjects applied the assigned study product topically to the axillary area once a day for 28 days. In 
Part 1 of the study, 24 subjects were enrolled (6 in each arm). These subjects underwent PK blood 
draws and additional ECG analysis. After an interim safety and tolerability analysis, an additional 
165 subjects were enrolled in Part 2 of the study. In total, 189 subjects were enrolled (ITT 

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population) at 12 study sites. Among the ITT population, 93.7% completed the study. Reasons for 
early discontinuation included withdrawal by subject (n=6), loss to follow-up (n=5), and AE (n=1). 
All concentrations of BBI-4000 gel were well tolerated locally. The incidence of local tolerability 
signs was low and generally similar among treatment groups; and most tolerability signs were 
minimal in severity, occurred bilaterally, and typically transient. The incidence of treatment-
emergent adverse events (TEAEs) was relatively low (21.2%), with the lowest incidence in the 
vehicle group (13.0%) and the highest in the 15% gel group (29.2%). Most TEAEs were mild in 
severity (63.8%) and were considered to be possibly, probably, or definitely related to treatment 
(66.7%). The most common TEAEs included dry mouth (4.2%), vision blurred (3.7%), and 
application site pain (2.6%). Observed systemic TEAEs were consistent with known adverse 
effects of drugs of this class (i.e., anti-cholinergic activity). There were no reported SAEs or 
deaths.  
Overall, treatment with BBI-4000 15% gel demonstrated a significant improvement in efficacy 
variables compared to the vehicle gel at Day 29 (end of therapy [EOT]), with less marked 
improvement at Day 42. For the primary endpoint (t2-point improvement in HDSS at Day 29), 
there was a statistical difference (p=0.044) among the 4 groups, with the active treatment groups 
having directionally better outcomes compared to the vehicle group. In addition, a significantly 
(p=0.010) higher proportion of subjects in the 15% gel group (38.3%) had a t2-point improvement 
in HDSS at Day 29 compared with the vehicle group (12.2%). Improvement in efficacy variables 
in the 15% gel group was greater than that of the lower concentrations of BBI-4000 gel and the 
vehicle gel, with trends for larger improvement with increasing concentrations of BBI-4000 (i.e., 
dose-response) for some endpoints. 
Systemic exposure of BBI-4000 and its metabolite, BBI-4010, was minimal following the first 
dose and after multiple doses of BBI-4000 gel, with higher plasma concentrations observed in the 
15% gel group. After multiple doses of 5% or 10% gel, absorption of BBI-4000 remained low; PK 
parameters were calculable for a single 5% gel subject (mean Cmax=0.4460 ng/mL, median Tmax=1 
hr) and for a single 10% gel subject (mean Cmax=0.7860 ng/mL, median Tmax=1 hr). After multiple 
doses of 15% gel, measurable BBI-4000 concentrations were observed on Days 8, 15, and 25. For 
BBI-4000 15% gel group, mean Cmax was 1.831 ng/mL with a median Tmax of approximately 3 
hours and AUC0-last of 16.03 hr•ng/mL. After the first dose of BBI-4000, plasma concentrations of 
BBI-4010 were BLQ for all subjects, except one (15% gel). After multiple BBI-4000 doses, BBI-
4010 Cmax was 0.5038 ng/mL with a median Tmax of approximately 4 hours and AUC0-last of 
5.283 hr•ng/mL.  
Study BBI-4000-CL-202  
This was a Phase 2, multicenter, randomized, double-blind, vehicle-controlled, parallel-group 
study of BBI-4000 15% DB20 gel conducted in 50 subjects with primary palmar hyperhidrosis. 
The objectives of this study were to assess the safety, local tolerability, and effect of BBI-4000 
15% gel on sweat production. This study was not powered to show statistically significant 
differences in the efficacy endpoints. 
Subjects were randomized to either BBI-4000 15% gel (n=25) or vehicle gel (placebo; n=25), and 
applied the assigned product to the palms of both hands once daily for 28 days. Of the ITT 
population (N=50), 86.0% completed the study. Reasons for discontinuation included lost to 

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follow-up (n=2), non-compliance with study drug (n=1), withdrawal by subject (n=1), AE (n=1), 
and other (n=2). 
BBI-4000 15% gel was well tolerated. The incidence of local tolerability signs was low, and most 
tolerability signs were minimal to mild in severity, occurred bilaterally, and typically transient. 
Burning and itching were somewhat more frequent in the 15% gel group than the vehicle gel 
group; dryness was most frequent in the 15% gel group, with fewer subjects having erythema in 
both groups. The incidence of TEAEs was relatively low (24.5%), with a higher incidence in the 
15% gel group (33.3%) than in the vehicle group (16.0%). The majority of AEs were mild in 
severity. The most common TEAEs included dry mouth (8.3%) and mydriasis (8.3%). Observed 
systemic TEAEs were consistent with known adverse effects of drugs of this class (i.e., anti-
cholinergic activity). There were no SAEs or deaths. 
Measures associated with sweat production included direct measurement of sweat production 
(gravimetric assessments) by the investigator and subjective assessments by the subjects (HDSS, 
Hyperhidrosis Disease Severity Measure-Palm scale (HDSM-Palm), Palmar Hyperhidrosis Impact 
Scale [PHIS], and modified Dermatology Life Quality Index-Palm [DLQI-Palm]). The primary 
efficacy objective was to assess the effect of BBI-4000 15% gel on sweat production. Although 
there were no significant differences between 15% gel and vehicle gel groups in any of the 
efficacy measures, the reduction in sweat production measured gravimetrically across multiple 
time points was more evident in the 15% gel group, though this decrease was not maintained at 
Day 29.  
Additional ad hoc analysis was conducted to investigate 4 different criteria for treatment success in 
the BBI-4000 15% gel and vehicle gel groups (ITT population). This analysis demonstrated a trend 
for efficacy of BBI-4000 15% gel compared to the vehicle gel.  
Study BBI-4000-CL-103  
This was a Phase 1, single-center, 3-cohort, open-label, repeat-dose, PK, safety and tolerability 
study of 5% BBI-4000 isopropyl myristate (IPM) gel, 15% BBI-4000 IPM gel, and 15% BBI-4000 
Dimethiconol Blend 20 (DB20) gel formulations in 30 healthy subjects. The primary objective of 
this study was to evaluate the PK profile of BBI-4000 and its metabolite, BBI-4010, following 
topical dosing. The secondary objective was to assess the safety and tolerability of topical dosing 
of BBI-4000. 
Subjects were randomized to 1 of 3 cohorts (n=10 each): 5% IPM gel, 15% IPM gel; and 15% 
DB20 gel; and applied the assigned drug to axillae once daily for 14 days. Of the ITT population 
(N=30), 93.3% completed the study. Reasons for discontinuation included AE (n=1) and loss of 
consent (n=1).  
Overall, all BBI-4000 gel treatments were well tolerated, and reported AEs were mild to moderate. 
The incidence of TEAEs was relatively low, with a higher incidence in the 15% IPM gel group 
(n=26) compared to the other groups (5% IPM gel, n=11; 15% DB20 gel, n=9). A total of 46 AEs 
was reported by 15 subjects, and all but one of the reported AEs were mild in severity (moderate 
urinary retention). The observed systemic reactions were consistent with known adverse effects of 
drugs of this class (i.e., anti-cholinergic activity). There were no reported SAEs or deaths. 
The lower limit of quantification (LLOQ) was 0.0500 ng/mL for BBI-4000 and 0.100 ng/mL for 
BBI-4010. Quantifiable concentrations of BBI-4000 and BBI-4010 were observed in all 3 dose 
cohorts, allowing for calculation of Cmax and AUC0-t parameters.  

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x For BBI-4000, at Day 14, the mean Cmax value for 15% IPM gel (11.2 ng/mL) was 
approximately 5-fold greater than in 5% IPM gel (2.23 ng/mL) or 15% DB20 gel (2.39) 
ng/mL), both of which were comparable.   
x AUC0-t data support increased absorption of BBI-4000 with the IPM gel formulation. Day 
14 AUC0-t for 15% IPM gel formulation (119 hr.ng/mL) was approximately 4-fold greater 
than that of either 5% IPM gel (31.0 hr.ng/mL) or 15% DB20 gel (30.9 hr.ng/mL), which 
were comparable. 
x Similar trends were seen for BBI-4010, with an approximate 3-fold increase in Cmax, and 
over a 2-fold increase in AUC0-t values, for 15% IPM gel as compared to either the 5% 
IPM or 15% DB20 gel formulations. 
Both the Cmax and AUC findings in this study corroborate similar findings from a previous 
bridging toxicity study in minipigs, where toxicokinetics showed that BBI-4000 and BBI-4010 
plasma exposures were 2.8-fold and 2.0-fold higher, respectively, after topical application of a 
20% BBI-4000 IPM gel formulation in comparison to a 20% BBI-4000 DB20 gel formulation. 
 
Risks to Subjects 
As an anticholinergic drug, topical administration of BBI-4000 gel could be associated with signs 
or symptoms typical of a systemic anticholinergic effect such as dry mouth, blurred vision, 
dizziness, constipation, urinary retention, or tachycardia, among others.  The previous BBI-4000 
exposure to humans has demonstrated a low incidence of these effects and mild in severity. One 
subject who received BBI-4000 15% gel applied to the axillae in the Phase 2b (Study BBI-4000-
CL-201) and two subjects who received BBI-4000 5% and 15% gel applied to the axillae in the 
Phase 1 (Study BBI-4000-CL-103) withdrew from the study due to anticholinergic AEs; moderate 
blurred vision, headache, urinary hesitation, and application site dryness (BBI-4000 15% CL-201 
study); moderate urinary retention, mild dry eyes and dry mouth (BBI-4000 5% CL-103 study); 
and mild lightheaded and nausea (BBI-4000 15% CL-103 study). 
2 
STUDY DESIGN 
This is an outpatient Phase 2 confirmatory, multicenter, randomized, double-blind, vehicle-
controlled, parallel-group study comparing BBI-4000 5%, 10% and 15% gel containing IPM with 
vehicle (placebo) in subjects with axillary hyperhidrosis.   
A maximum of 220 subjects, at approximately 25 clinical sites, will be enrolled to obtain 
approximately 200 subjects that have completed dosing and critical assessments. 
Subjects will be randomized to receive BBI-4000 5%, or 10%, or 15% gel, or vehicle (placebo) gel 
in a balanced ratio of 1:1:1:1. 
Subjects will apply the investigational product (BBI-4000 5%, 10% and 15% gel or vehicle; 
approximately 50 subjects per cohort) once daily at bedtime, to their axillae for 42 consecutive 
days. 
Patient-reported outcomes (HDSM-Ax, HDSS & DLQI) and Gravimetric assessments will be 
recorded during the study at predefined time points. Vital signs, local tolerability assessments 
(including, burning, itching, dryness, scaling and erythema assessed using standardized scales) and 
adverse events will be collected at each visit.  

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A urine pregnancy test (UPT) in females of child-bearing potential; and blood and urine samples 
will be collected and analyzed at the Screening Visit and at the End of Treatment Visit for routine 
hematology, chemistry, and urinalysis parameters. 
A total of 14 scheduled visits will take place over approximately 12 to 16 weeks, depending on 
when the Baseline Visit (treatment) is scheduled after, and including, four (4) screening period 
visits:  initial screening, GSP1 and GSP2, and Rescreening GSP3.   
3 
STUDY OBJECTIVES AND ASSESSMENTS 
The purpose of this Phase 2 study is to assess the efficacy, safety, and local tolerability of the 
topical formulation BBI-4000 5%, 10% and 15% gel in subjects with axillary hyperhidrosis.  
3.1 
Study Objectives 
Primary: 
x To evaluate the effect of BBI-4000 5%, 10% and 15 % gel on Hyperhidrosis Disease 
Severity Measure (HDSM-Ax) when applied topically in subjects with axillary 
hyperhidrosis. 
x To evaluate the safety and local tolerability of BBI-4000 5%, 10% and 15% gel when 
applied topically in subjects with axillary hyperhidrosis. 
Secondary: 
x To evaluate the effect of BBI-4000 5%, 10% and 15% gel on hyperhidrosis disease severity 
as it relates to gravimetrically measured sweat production (GSP), patient reported 
Hyperhidrosis Disease Severity Score (HDSS) and Dermatology Quality of Life Index 
(DLQI) self-assessment. 
3.2 
Study Assessments 
Efficacy Assessments: 
The following assessment measures will be conducted to evaluate the efficacy of BBI-4000 
x Hyperhidrosis Disease Severity Measurement-Axillary (HDSM-Ax) as measured by the 
subject 
x Gravimetrically measured sweat production (GSP) by the investigator 
x Hyperhidrosis Disease Severity Scale (HDSS) as measured by the subject 
x Dermatology Life Quality Index (DLQI) as measured by the subject 
 
Safety Measures: 
The following safety assessment measures will be conducted: 
x Adverse events  
x Local tolerability assessments including burning, itching, dryness, scaling and erythema 
x Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) 
x Laboratory tests (hematology, chemistry, and urinalysis) and pregnancy testing in females 
of child bearing potential 

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4 
STUDY POPULATION 
4.1 
Number of Subjects  
A maximum of 220 subjects will be enrolled at approximately 25 study sites to obtain 
approximately 200 subjects that have completed dosing and critical assessments.   
4.2 
Inclusion Criteria 
Subjects must fulfill all of the following criteria to be eligible for study admission: 
1. Male or female subject ≥ 18 years of age in good general health. 
2. Diagnosis of primary axillary hyperhidrosis in the opinion of the Investigator that meets all 
the following criteria: 
a. HDSM-Ax of 3 – 4 inclusive at both of the Screening visits (Visit 1 and 4) (see 
Appendix 3). 
b. Gravimetric test indicating a minimum of 50 mg of sweat production at rest in each 
axilla with a two-axilla combined total of at least 150 mg of sweat production in 
five (5) minutes (at room temperature, 20oC to 25oC (68oF to 77oF)) at Screening 
Visit 1 and at least one of Visits 2, 3 or 4.  
c. HDSS of 3 or 4 at both of the Screening visits (Visit 1 and 4) (see Appendix 2). 
d. Symptoms of axillary hyperhidrosis for at least 6 months’ duration  
3. The ability to understand and sign a written informed consent form (ICF), which must be 
obtained prior to any study-related procedures (including medication wash-out, if required) 
and treatment. 
4. The ability to understand and sign a Health Insurance Portability and Accountability Act 
(HIPAA) authorization form which shall permit the use and disclosure of the subject’s 
individually identifiable health information. 
5. The ability to understand and follow all study-related procedures including study drug 
administration.  
6. Sexually active female of childbearing potential (FOCBP)* must agree to periodic 
pregnancy testing and use a medically acceptable method of contraception while receiving 
protocol-assigned product. This includes perimenopausal women who are less than 12 
months from their last menses. Acceptable contraceptive methods include the following:  
x Abstinence for the duration of the study or where partner is sterile (e.g., vasectomy) is 
acceptable form of contraception 
x Hormonal contraception, including oral, injectable, or implantable methods started at 
least 2 months prior to screening, OR 
x Two forms of non-hormonal contraception, including intrauterine devices (at least 1 
week status post placement), or properly used barrier methods (e.g., male or female 
condoms, cervical cap/diaphragm, spermicidal agents, etc.). 
*  Female of childbearing potential for this study includes any female 18 years of age or 
older who has not undergone successful surgical sterilization (hysterectomy, bilateral 

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tubal ligation (at least six months prior to baseline) or bilateral oophorectomy) or is not 
postmenopausal (defined as amenorrhea greater than 12 consecutive months in women 
55 years or older).  
4.3 
Exclusion Criteria 
The following criteria will exclude a subject from participating in this study: 
1. In the Investigators opinion, any skin or subcutaneous tissue conditions of the axilla(s), 
(i.e., the axillary area should be deemed otherwise “normal”, besides the hyperhidrosis 
diagnosis, and free of blisters, large boils or sinus tracts, significant scarring or open 
wounds). 
2. Prior use of any prohibited medication(s) or procedure(s) within the specified timeframe 
for the treatment of axillary hyperhidrosis: 
a. Botulinum toxin to the axillary area within 9 months of GSP1 (Visit 2). 
b. Axillary thermolysis, sympathectomy or surgical procedures of the axillary area at any 
time in the past. 
Prior axillary laser hair removal is permitted if more than 7 days prior to GSP1  
(Visit 2). 
c. Serotonergic agonist (or drugs that increase serotonin activity including SSRIs), beta-
blocker, alpha-adrenergic agonist (clonidine), dopamine partial agonist or tricyclic 
antidepressant treatment within 30 days of GSP1 (Visit 2).  
However, if a subject has been on a stable dose (in the opinion of the PI) of any of these 
medications and has not had a recent change in hyperhidrosis frequency or severity for 
3 months prior to the baseline visit; they may be included.  Doses of these agents 
should not be altered during the course of the study. 
d. Any topical prescription treatment for hyperhidrosis within 30 days of GSP1 (Visit 2). 
e. Any over-the-counter topical antiperspirant/deodorant (applied directly to the axilla(s)) 
within 7 days of GSP1 (Visit 2). 
3. Anticholinergic agents used to treat conditions such as, but not limited to, hyperhidrosis, 
asthma, incontinence, gastrointestinal cramps, and muscular spasms by any route of 
administration (e.g. IV, oral, inhaled, topical, etc.) within 30 days of GSP1 (Visit 2).   
4. Use of potent inhibitors of cytochrome P450 CYP3A and CYP2D6, (see Appendix 7) 
within 14 days prior to GSP1 (Visit 2). The use of topical antifungal medications is 
permitted if not applied in the treatment area. 
5. Any oral or topical homeopathic or herbal treatment (i.e. alternative therapies such as sage 
tablets, chamomile, valerian root and St. John’s Wort) within 15 days of GSP1 (Visit 2). 
6. Use of any cholinergic drug (e.g. bethanechol) within 30 days of GSP1 (Visit 2). 
7. Use of any anti-anxiety and/or anti-depressant, amphetamine product or drugs with known 
anticholinergic side effects is prohibited with the following exceptions: 

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a. If a subject has been on a stable dose of an anti-anxiety and/or anti-depressant drug and 
has not had a recent change in hyperhidrosis frequency or severity for 3 months; they 
may be included.   
b. An amphetamine product may be allowed if the dose has been stable for at least 6 
months without change in hyperhidrosis frequency or severity. 
c. Drugs with known anticholinergic side effects (taken within the last 30 days) including 
dry mouth, blurred vision may be allowed based on the principal investigator’s 
assessment. 
NOTE:  If anticholinergic side effect(s) are experienced on these medications prior to 
starting study medication; document the side effect(s) and severities in the source 
document and the eCRF. 
The doses of these agents should not be altered during the course of the study. 
8. Known cause of hyperhidrosis or known history of a condition that may cause 
hyperhidrosis (i.e., hyperhidrosis secondary to any known cause such hyperthyroidism, 
diabetes mellitus, medications, etc.). 
9. Subject with hyperhidrosis symptoms initiated or exacerbated with their menopause. 
10. Subjects with unstable type 1 or type 2 diabetes mellitus or thyroid disease, history of renal 
impairment, hepatic impairment, malignancy, glaucoma, intestinal obstructive or motility 
disease, obstructive uropathy, myasthenia gravis, benign prostatic hyperplasia (BPH), 
neurological conditions, psychiatric conditions, Sjögren’s syndrome, Sicca syndrome, or 
cardiac abnormalities that may alter normal sweat production or may be exacerbated by the 
use of anticholinergics in the investigator’s opinion. 
11. Subjects with known hypersensitivity to glycopyrrolate, anticholinergics, or any of the 
components of the topical formulation. 
12. Subject is pregnant, lactating or is planning to become pregnant during the study.  
13. Participating in or used an investigational drug or device within 30 days prior to GSP1 
(Visit 2). 
14. Any major illness within 30 days before the screening examination. 
15. Any other condition including psychiatric illness (depression and/or anxiety) that would 
interfere with study participation and/or evaluation of study endpoints or laboratory 
abnormality that, in the opinion of the investigator, would put the subject at unacceptable 
risk for participation in the study or may interfere with the assessments included in the 
study. 
16. History or presence of supraventricular tachycardia, ventricular arrhythmias, atrial 
fibrillation or atrial flutter. 
17. Employees of Brickell Biotech, Inc., the investigator, or contract research organization 
(CRO) involved in the study, or an immediate family member (partner, offspring, parents, 
siblings, or sibling’s offspring) of an employee involved in the study. 
 

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Protocol BBI-4000-CL-203 
Page 25 of 65 
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22 February 2017 
5 
INVESTIGATIONAL PRODUCT (IP) 
BBI-4000 (sofpironium bromide) Gel is a clear to slightly translucent colorless gel and is packaged 
in a white colored, metered pump container.  Two pump containers are packaged in a carton with 4 
applicators.  The total gel volume in each container is 45 mL (~ 40 g).  The gross weight of each 
full container at baseline is approximately 74 to 80 grams.  BBI-4000 (sofpironium bromide) Gel 
is an anhydrous gel formulation containing the drug substance in a gel base comprising 
hydroxylpropyl cellulose NF, hexylene glycol NF, isopropyl myristate NF, citric acid anhydrous 
USP, and alcohol dehydrated USP.   
Each pump container is sufficient for 21 days of dosing, per protocol instructions.  One pump 
actuation delivers ~ 0.67 mL of the gel formulation. 
BBI-4000 vehicle (placebo) gel will be identical in appearance and constituents to BBI-4000 
(sofpironium bromide) Gel, but will not contain the active ingredient, BBI-4000.  Two placebo 
pump containers are packaged in a carton with 4 applicators to match the active drug product kits. 
5.1 
Methods for Masking/Blinding 
The investigational materials will be packaged in identical-appearing pump containers in the same 
white cartons, each with four (4) applicators. The product will be identified as an investigational 
compound. The randomization number will be identified on each unit label.  The investigational 
materials (i.e. each pump container and outer carton) will be labeled with panel labels.   
The outer carton will be labeled with a 2-part tear-off label which includes the blind-break panel. 
The first panel is permanently adhered to the carton and should not be removed.  The tear-off 
portion with the blind-break panel will be separated along the label perforation and placed into the 
study subject source file.  The blind-break panel will have a scratch-off area that can be removed, 
if needed, to reveal the specific product [i.e. active (corresponding strength) or placebo (vehicle)] 
provided to the study subject.   
Each pump will have 2 labels: A one-panel label corresponding to the carton label and a second 
smaller label on which the subject number and initials should be recorded.  
Example labels are provided below 
1st Panel Adhered to Carton 
Blind Break Panel to be Removed and Placed in Subject File 
 
 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 26 of 65 
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22 February 2017 
Panels Adhered to Pumps 
   
 
 
5.2 
Storage of Investigational Product  
The investigational product must be stored in a secure area with access limited to the investigator 
and authorized site staff and administered only to subjects entered into the clinical study, at no cost 
to the subject, in accordance with the conditions specified in this protocol. 
Investigational product should be stored at controlled room temperature 68oF to 77oF (20oC to 
25oC) with excursion permitted between 59°F to 86°F (15oC to 30oC). Maintenance of a 
temperature log (manual or automated) is required.   
5.3 
Instructions for Use and Administration of Investigational Product 
The investigational product kit carton will be provided to each site and will include two individual 
plastic pump containers in one carton. Each carton will also contain 4 applicators.  Each 
investigational plastic pump container will contain sufficient drug product for a 21-day treatment 
period.   
Each carton will have a unique randomization number printed on the label and each of the two 
pump container labels will display the same unique randomization number. 
Each subject will be randomized to receive BBI-4000 (sofpironium bromide) Gel 5%, or 10%, or 
15%, or Vehicle to apply, once a day, to each axilla (1 pump per axillae) using the supplied 
applicators for 42 consecutive days.   
Subjects will be instructed to apply the investigational product to each axilla with one full 
actuation of the pump for each dose application.  Each actuation of the pump corresponds to 
approximately 0.56 grams (i.e., 0.67 mL) of investigational product.   
The subject will apply all doses of investigational product at night, prior to going to bed with the 
supplied applicators.  Subjects will apply their first dose of gel prior to bedtime the night of their 
Baseline Visit.  The subject should be instructed to use their investigational product each night 
with the last application the night before attending the end of-treatment evaluation (i.e., Day 43 
visit).  Subjects should wash the applicator each night after dosing.  Four applicators are provided 
in each kit to compensate for loss or damage during handling; it is not necessary to use all 4 
applicators over the specified dosing interval. 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
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22 February 2017 
To ensure accurate dosing, the Study Staff will be instructed to prime the pump container before 
dispensing to the subject by pressing the pump for three (3) sequential actuations and to discard to 
waste any dispensed gel from these 3 priming actuations.   
The weight of the pump container with the cap on will be recorded after priming and will then be 
dispensed to the subject. Container 1 of 2 will be primed/weighed and then dispensed at the 
Baseline Visit along with the 4 applicators, and Container 2 of 2 will be primed/weighed/dispensed 
at Day 22 (Visit 8). Container 1 of 2 will be returned by the patient and weighed at Day 22 (Visit 
8) and Container 2 of 2 will be returned by the patient and weighed at the End of Treatment Visit. 
At Visit 8 (Day 22) and Visit 13 (Day 43, End of Treatment), the dispensed pump (Container 1 of 
2 and 2 of 2 respectively) will be collected from the subject, weighed and compliance will be 
discussed and documented.  Study subjects may return the applicators, or they may discard them 
after dosing is complete. 
5.4 
Instructions for the Subjects 
Subjects will be instructed to apply the investigational product every day, at night prior to bedtime 
using a supplied applicator as follows (a written instruction sheet will be supplied to the Subject): 
1. Expose the underarm areas and ensure they are dry. Don’t wash the underarm areas prior to 
drying (no washing up to 30 minutes prior to drug application).  
2. Carefully, by slowly applying pressure to the actuator with an index finger, place the gel of 
ONE full actuation onto the dome of the white plastic applicator.  
3. Take the applicator using the three (3) middle fingers of the left hand in the plastic applicator 
hole and immediately apply study product to the right underarm area. 
4. Distribute the product using the plastic applicator in a way that covers all the underarm area 
where the hair grows by gently applying a layer of the product. 
5. Repeat the procedure to apply the study product to the left underarm using the right hand. 
6. Wash both hands and the plastic applicator thoroughly for about 2 minutes. 
7. Allow the study product to dry for 5 minutes before putting any clothes on over the treatment 
areas. 
Important information: 
x The subject should sleep in a T-shirt or similar loose fitting top to avoid touching the underarm 
area while sleeping. 
x Subjects should maintain their underarm areas grooming habits but should not shower, shave, 
or wash the underarm area for at least 8 hours after study product application. If the subject 
takes a shower, shaves or washes the underarm area at night, then the subject should wait at 
least 30 mins before study product application. Ensure the underarm areas are dry before study 
product application. 

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Protocol BBI-4000-CL-203 
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22 February 2017 
x Subjects should not apply any other product to the axillary area (including sponsor supplied 
deodorant which should be used in the morning) for at least 8 hours after study product 
application.  
x The subject should use the applicator provided to avoid contact with skin of the hands.  Special 
care should be taken to avoid contact of the gel with the eyes or mouth. Of note, hands should 
be washed for about 2 minutes after applying the gel to avoid possible skin and eye contact 
with the gel. 
x The study product contains alcohol and is flammable.  The subject should avoid fire, flame or 
smoking during study product application and until the gel has dried.  The subject should not 
expose the container to fire, flame or extreme heat. 
On the day of a clinic study visit:  
x Showering in the morning is permissible. 
x Do not apply any product to the axilla (including sponsor-supplied deodorant). 
x Exercise is to be avoided (e.g., gym, jogging, etc.). 
x Avoid caffeine and tea until the gravimetric assessments are completed.  
6 
CONCOMITANT MEDICATIONS/TREATMENTS 
Information on concomitant medications/treatments (e.g. aspirin, Tylenol, birth control pills, IUD, 
vitamins) taken during study participation, or which require a washout for study participation will 
be recorded. Every effort should be made to keep dosing with any concomitant medications 
consistent /constant during the study.  
6.1 
Permissible Medications/Treatments 
Therapy considered necessary for the subject's welfare may be given at the discretion of the 
investigator.  If the permissibility of a specific medication/treatment is in question, the Medical 
Monitor should be contacted. 
Subjects will be instructed to not apply any topical product to their axillary area (e.g., 
antiperspirants, creams, etc.), with the exception of the use of the sponsor-supplied deodorant.   
The deodorant should not be applied within 8 hours following the application of study product 
(suggest applying in the morning). 
6.2 
Prohibited Medications/Treatments 
The decision to administer a prohibited medication/treatment is made with the safety of the study 
participant as the primary consideration.  When possible, the Medical Monitor and Brickell 
Biotech should be notified before a prohibited medication/treatment is administered.  
Prior to the inclusion of a subject in the study, as specified in Section 4.2 and 4.3 (I/E criteria), 
and throughout the duration of the study, the use of the following medications/treatments is 
prohibited: 
x Anticholinergic agents used to treat conditions such as, but not limited to, hyperhidrosis, 
asthma, incontinence, gastrointestinal cramps, and muscular spasms by any route of 
administration (e.g. IV, oral, inhaled, topical, etc.).   
 

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22 February 2017 
x Any oral or topical homeopathic or herbal treatment (i.e. alternative therapies such as sage 
tablets, chamomile, valerian root and St. John’s wart). 
x Any topical product(s) including but not limited to cosmetics, prescription products, 
antiperspirants/deodorants or similar agents (e.g., Drysol, Xerac AC, Certain DRI, etc.) and 
hand sanitizers applied to the axillae for the duration of the study.   
x Any treatment or procedure for axillary hyperhidrosis including but not limited to: 
o botulinum toxin  
o thermolysis treatments including microwave (e.g. MiraDry), laser or other(s)  
o sympathectomy 
x Any surgical procedure involving the axillae (including laser hair removal), or any surgical 
procedures that will result in significant scarring of the axillae. 
x Any oral cholinergic (e.g. bethanechol) throughout the duration of the study. 
x Addition of, or change of dose for any medication that is allowed as specified in  
Section 4.2 and 4.3 (I/E criteria) including serotonergic agonists (or drugs that increase 
serotonin activity including SSRIs), beta-blockers, alpha-adrenergic agonist (clonidine), 
dopamine partial agonists, tricyclic antidepressants, anti-anxiety and/or other anti-depressant 
drugs, amphetamine products and drugs with known anticholinergic side effects. 
Since no drug-drug interaction studies have been conducted to evaluate whether concomitant 
medications affect BBI-4000, potent inhibitors of CYP3A and, CYP2D6  should not be 
administered as specified in Section 4.3 and 4.2 (I/E criteria): see Appendix 7 
7 
PROCEDURES 
The timing of each assessment is listed in the Time and Events Table (Section 7.1).   
Gravimetric assessments will be conducted between 7:00am - 11:00am.  
Each subject will report for 14 distinct visits.  
All Screening assessment results must be completed and reviewed prior to the Baseline Visit.  
Therefore, none of the Screening Visit days can occur on the same day as the Baseline Visit. 
Subjects may be consented for up to 56 days before the Baseline Visit.  Subjects outside this 
screening window shall be re-consented and certain screening activities may need to be repeated.  
Prior to enrollment into the treatment phase of the study, the Investigator or designee will contact 
the Medical Monitor to address such subjects on a case-by-case basis. 
Subjects who require a protocol-specified washout (see Section 4.3) must be consented at the time 
of stopping the medication. Washouts must be completed prior to Visit 2 (GSP 1) (i.e. within 35 
days of the Screening Visit). In the event a subject does not satisfy the sweat production eligibility 
(Inclusion criteria 2b) at the Screening Visit, but is otherwise eligible to continue (i.e., satisfies all 
other eligibility requirements including HDSM-Ax and HDSS severity but may still require a 
washout), the Screening GSP may be retested once during the screening period at the discretion of 
the Investigator.  
 
 

BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 30 of 65 
CONFIDENTIAL 
22 February 2017 
7.1 
Time and Events Table 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
PROCEDURE 
Screening 
Rescreening 
Baseline 
 
 
End of 
Treatment 
Follow-up 
Gravimetric Timepoint 
 
GSP 
1 
GSP 
2 
GSP 
3 
 
 
 
 
 
 
GSP 
4 
GSP 
5 
GSP 
6 
 
Day  
(allowable window) 
Up to 
35 days 
prior to 
GSP1  
Up to 14 days 
from  
GSP1 to GSP3  
Day 1  
(within  
7 days of 
Rescreening) 
Day  
8  
(± 2) 
Day 
15  
(± 2) 
Day 
22  
(± 2) 
Day 
29  
(± 2) 
Day 
36  
(± 2) 
Day 
41  
(±2) 
Day 
42  
(± 2) 
Day 
43  
(± 2) 
Day 
57  
(± 3) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History, demographics 
X 
 
 
X  
 
 
 
 
 
 
 
 
 
Physical Exam  
 
 
 
X  
 
 
 
 
 
 
 
 
 
Vital Signs (blood pressure, heart 
rate, respiratory rate and 
temperature) 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
I/E Criteria 
X 
 
 
X  
 
 
 
 
 
 
 
 
 
Gravimetric Assessments a, b 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
HDSM-Ax, HDSS 
X 
 
 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI 
 
 
 
X  
 
 
 
 
 
 
 
X 
 
Local Tolerability Assessments c 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Adverse Events c   
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization d 
 
 
 
X  
 
 
 
 
 
 
 
 
 
Investigational Product e (IP) 
Dispensed / Returned 
 
 
 
 
Xf 
 
 
Xf  
 
 
 
X 
 
IP Weight g 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
 
Compliance Evaluation 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Safety Labs (hematology, 
chemistry, and urinalysis) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
UPT (females of childbearing 
potential only)h 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Concomitant Medication Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a) Gravimetric assessments for all visits will be conducted from 7:00am-11:00am. 
b) One 5-minute gravimetric assessment will be conducted for each axilla. See section 4.2 (2b) for gravimetric assessment 
inclusion criteria. 
c) Investigator assessments to be performed after the Subject assessments. 
d) Randomization will take place only after the subject is qualified at the rescreening visit.  
e) Order the investigational product only after the subject is qualified at the rescreening visit and randomized.  
f) 
Pump 1 of 2 to be dispensed at Baseline (Visit 5). At Day 22 (Visit 8) Pump 2 of 2 to be primed and dispensed to 
patient. Written instructions for nightly dosing will be given to the subject.  Subjects will apply their first dose of gel 
prior to bedtime the night of their Baseline visit. Instruct the subjects to return Pump 1 of 2 at Day 22 Visit 8 and Pump 
2 of 2 at Day 43 (Visit 13, End of Treatment).   
g) Pump container 1 of 2 will be weighed after priming at Baseline prior to dispensing to the subject and upon return at 
Day 22 (Visit 8). Pump container 2 of 2 will be weighed after priming at Day 22 (Visit 8) prior to dispensing to the 
subject and upon return at Day 43 (Visit 13, End of Treatment).   
h) FOCBP for this study includes any female 18 years of age or older who has not undergone successful surgical 
sterilization (hysterectomy, bilateral tubal ligation [at least six months prior to baseline] or bilateral oophorectomy) or is 
not postmenopausal (defined as amenorrhea greater than 12 consecutive months in women 55 years or older).   

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22 February 2017 
7.2 
Visit-Specific Procedures 
7.2.1 
Visit 1 (Screening) 
Written informed consent must be obtained prior to any study-related procedures. Potential 
subjects will be screened within 35 days prior to Visit 2 (GSP1) to assess their eligibility to enter 
the study. Only eligible subjects with axillary hyperhidrosis will be enrolled.  
After informed consent is obtained, the following procedures will be performed: 
x Collect and review subject medical history and demographics. 
x Review concomitant medications/treatments and assess for washouts. 
x Assess inclusion/exclusion criteria.  
x Subject to complete the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) 
assessment. 
o Six multi-part questions to be completed by the subject prior to other assessments 
o Refer to Appendix 3 
x Subject to complete the Hyperhidrosis Disease Severity Scale (HDSS) assessment 
o Refer to Appendix 2 
x Perform Gravimetrically measured Sweat Production (GSP). 
o Gravimetric assessment must occur between 7:00 am-11:00 am.  
o Refer to Appendix 1 for instructions and requirements of sample collection and 
handling 
x Collect samples for laboratory assessments (hematology, chemistry and urinalysis). 
x Perform Urine Pregnancy Testing (UPT) if applicable (FOCBP only). If positive, the 
subject shall be screen failed.  
x Provide subject with the sponsor-provided non-antiperspirant deodorant. Resupply as 
needed throughout subject study participation. 
x Schedule the subject to return for Visit 2 (GSP1) after any washout has been completed; 
must be within 35 days of Visit 1 (Screening). 
 
In the event a subject does not satisfy the sweat production eligibility (Inclusion criteria 2b) at the 
Screening Visit, but is otherwise eligible to continue (i.e., satisfies all other eligibility requirements 
including HDSM-Ax and HDSS severity but may still require a washout), the Screening GSP may 
be retested once during the screening period at the discretion of the Investigator:  
x Retest must occur within the 35-days from Screening (Visit 1) and must occur prior to 
GSP1 (Visit 2).  
x HDSM-Ax and HDSS must also be completed at the time of the Screening GSP retest.  
x If subject does not meet inclusion based on GSP, HDSM-Ax and HDSS results at the time 
of the retest, the subject shall be screen failed and may not be rescreened. 
 
Visits 2 through 4 will occur as separate visits between -1 to -day-14 after the initial screening 
visit (Visit 1).  
The subject shall be reminded that, on the day of each clinic study visit:  
x Showering in the morning is permissible. 

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22 February 2017 
x Do not apply any product to the axilla (including sponsor-supplied deodorant). 
x Exercise is to be avoided (e.g., gym, jogging, etc.). 
x Avoid caffeine and tea until the gravimetric assessments are completed.  
7.2.2 
Visit 2 (GSP1) and Visit 3 (GSP2) – during Screening period  
Any washouts required for prohibited medications (See section 4.3) must be completed prior to 
Visit 2 (GSP1). GSP assessments 1, 2 and 3 must be conducted on separate days.  
The following activities will be conducted: 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
7.2.3 
Visit 4 (Rescreening, GSP3) – during Screening period. 
No more than 14 days may elapse between Visit 2 (GSP1) and Visit 4 (Rescreening, GSP3).   
The following activities will be conducted: 
x Confirm subject medical history and demographics. 
x Perform physical exam including collection of height and weight (see Section 8.2.1). 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Subject to complete the Dermatology life quality Index-Axilla (DLQI) questionnaire. 
o 10 questions to be completed by the subject. 
o Refer to Appendix 4 
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Review inclusion/exclusion criteria to confirm eligibility 
o If subject eligibility is confirmed, contact Cu-Tech (CRO) to request 
Randomization Number assignment and shipment of subject’s assigned product. 
o Is subject eligibility is not confirm, the subject shall be screen failed. 
x Schedule the subject to return for Baseline within 2-7 days of Visit 4 (Rescreening).  
7.2.4 
Visit 5 (Baseline, within 2-7 Days after Rescreening/Visit 4)  
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Perform local tolerability assessments (see Section 8.2.6). 

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22 February 2017 
x Perform a UPT if applicable (FOCBP only). If positive, the subject shall be Early 
Terminated. 
x Confirm the randomization number assigned to the subject corresponds to the kit received. 
x Remove the tear-off unblinding panel from the kit carton and place in the subject’s source 
records. 
x Dispense study product container 1 of 2 to the subject: 
o Write patient number and initials on the study product container label. 
o Prime the pump (3 actuations) and discard expressed gel.  
o Weigh the primed pump and record in source prior to dispensing to the subject. 
Dispense the pump to the subject in the kit carton with the included 4 applicator 
o Provide subject with patient study drug application brochure, access to a study 
product application video and digital mobile application. 
o Review with subject the study drug application procedure (Refer to Appendix 6). 
o Instruct subject to apply the first application of study medication at home the 
evening of Visit 5 (Baseline). 
o Confirm the subject has adequate supply of the sponsor-provided non-antiperspirant 
deodorant and resupply as needed. 
o Subject should be reminded to bring their study medication with them to Visit 8 
(Day 22).  
x Schedule the subject to return for the next study visit. 
7.2.5 
Visit 6 (Day 8 ±2) and Visit 7 (Day 15 ±2)  
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Perform local tolerability assessments. 
x Evaluate subject compliance: 
o Ask subjects if they applied the study product to the right and left axilla each 
evening as directed and confirm reason for any missed doses. 
o Verbally confirm application process.  
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Schedule the subject to return for the next study visit. At Visit 7 (Day 15) remind the 
subject to bring pump container 1 of 2 to Visit 8 (Day 22). 
7.2.6 
Visit 8 (Day 22 ±2)  
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 

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22 February 2017 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Perform local tolerability assessments. 
x Collect subject’s study product container 1 of 2, weigh and record weight of container. 
x Evaluate subject compliance: 
o Ask subjects if they applied the study product to the right and left axilla each 
evening as directed and confirm reason for any missed doses. 
o Verbally confirm application process.  
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Dispense study product container 2 of 2 to the subject 
o Write patient number and initials on the study product container label. 
o Prime the pump (3 actuations) and discard expressed gel.  
o Weigh the primed pump and record in source prior to dispensing to the subject. 
x Remind subject to bring their study medication at Visit 13 (Day 43). 
x Confirm the subject has adequate supply of the sponsor-provided non-antiperspirant 
deodorant and resupply as needed. 
x Schedule the subject to return for the next study visit. 
7.2.7 
Visit 9 (Day 29 ±2)  
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Perform local tolerability assessments. 
x Perform a UPT if applicable (FOCBP only). If positive, the subject shall be Early 
Terminated. 
x Evaluate subject compliance: 
o Ask subjects if they applied the study product to the right and left axilla each 
evening as directed confirm reason for any missed doses. 
o Verbally confirm application process.  
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Confirm the subject has adequate supply of the sponsor-provided non-antiperspirant 
deodorant and resupply as needed. 
x Schedule the subject to return for the next study visit. 

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22 February 2017 
7.2.8 
Visit 10 (Day 36 ±2)  
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Perform local tolerability assessments. 
x Evaluate subject compliance: 
o Ask subjects if they applied the study product to the right and left axilla each 
evening as directed and confirm reason for any missed doses. 
o Verbally confirm application process. . 
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Confirm the subject has adequate supply of the sponsor-provided non-antiperspirant 
deodorant and resupply as needed. 
x Schedule the subject to return for the next study visit. 
7.2.9 
Visit 11 (Day 41 ±2, GSP4) and Visit 12 (Day 42 ±2, GSP5) 
The following activities will be conducted: 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Evaluate subject compliance: 
o Ask subjects if they applied the study product to the right and left axilla each 
evening as directed and confirm reason for any missed doses. 
o Verbally confirm application process.  
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Confirm the subject has adequate supply of the sponsor-provided non-antiperspirant 
deodorant and resupply as needed. 
x Schedule the subject to return for the next study visit. Remind the subject to bring pump 
container 2 of 2 to Visit 13 (Day 43). 
7.2.10 
Visit 13 (Day 43 ±2, GSP6) / End of Treatment  
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 

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x Subject to complete the DLQI questionnaire. 
x Perform local tolerability assessments. 
x Perform a UPT if applicable (FOCBP only). If positive, the subject shall be Early 
Terminated. 
x Collect samples for laboratory assessments (hematology, chemistry and urinalysis). 
x Collect subject’s study product container 2 of 2, weigh and record weight of container. 
x Evaluate subject compliance: 
o Ask subjects if they applied the study product to the right and left axilla each 
evening as directed and confirm reason for any missed doses. 
o Verbally confirm application process.  
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Confirm the subject has adequate supply of the sponsor-provided non-antiperspirant 
deodorant and resupply as needed. 
x Schedule the subject to return for the next study visit. 
7.2.11 
Visit 14 (Day 57 ±3) / 2 Week Follow-up / End of Study 
The following activities will be conducted: 
x Collect vital signs (blood pressure, heart rate, respiratory rate and temperature) after subject 
has been seated for at least 2 minutes. 
x Review changes to the subject’s health (adverse events) and usage of concomitant 
medications/treatments. 
x Subject to complete HDSM-Ax assessment. 
x Subject to complete HDSS assessment. 
x Perform local tolerability assessments. 
x Perform GSP; gravimetric assessment must occur between 7:00 am-11:00 am. 
x Discharge subject from the study. 
7.3 
Unscheduled Visits 
If a subject is seen for an unscheduled visit, an assessment and record of AEs should be completed, 
as appropriate. Additional evaluations should be performed as necessary, and the appropriate CRF 
pages should be completed. 
7.4 
Early Discontinuation of Subjects 
It is the right and duty of the investigator to discontinue a subject’s participation if the subject's 
health or wellbeing is threatened by continuation in the study. In the event of premature 
discontinuation, the investigator should determine the primary reason for discontinuation. A 
subject may be discontinued from the study if any of the following circumstances occur: 
x The subject experiences a serious adverse event (SAE) rendering them unable to continue 
study participation. 
x The subject experiences an AE that in the opinion of the investigator may pose a significant 
risk for continued participation of the subject in the study. 

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x The subject is unable to physically or mentally tolerate the use of the test investigational 
product. 
x An exclusion criterion becomes apparent at any time during the study; contact the sponsor or 
medical monitor to discuss prior to discontinuing subject participation.  
x The subject is not compliant with the study procedures; contact the sponsor or medical monitor 
to discuss prior to discontinuing subject participation. 
x The subject voluntarily withdraws from the study. When possible, document the reason the 
subject withdrew consent.  
x If for any reason per the Investigator’s or Brickell’s judgment, discontinuation is in the 
subject’s best interest. 
x If the subject becomes pregnant. 
Subjects who discontinue the study prior to the completion of all treatment visits will be asked to 
complete the evaluations corresponding to Visit 13 (Day 43, End of Treatment). The sponsor will 
be notified of early discontinuation as soon as possible during the study.  
8 
RESPONSE MEASURES AND SUMMARY OF DATA COLLECTION 
METHODS 
8.1 
Efficacy Measures 
The following assessment measures will be conducted to evaluate the efficacy of BBI-4000 as 
indicated in the Procedures Section 7.1: 
x Hyperhidrosis Disease Severity Measurement-Axillary (HDSM-Ax) as measured by the 
subject 
x Hyperhidrosis Disease Severity Scale (HDSS) as measured by the subject 
x Dermatology Life Quality Index (DLQI) as measured by the subject 
x Gravimetrically measured sweat production (GSP) as measured by the investigator 
 
Subjects must complete self-assessments prior to assessments being made by the investigator. 
Please see Appendices 1, 2, 3 and 4 for a full description of these assessments. 
8.2 
Safety Measures 
The following safety assessment measures will be conducted as indicated in Section 7.1, Time and 
Events Table. 
8.2.1 
Physical Exam 
An abbreviated physical examination will be conducted at Rescreening (Visit 4) and will include 
assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, 
abdomen (liver and spleen), lymph nodes and extremities.  Height and weight will also be 
measured and recorded. 

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8.2.2 
Vital Signs 
Subjects should be seated for at least 2 minutes prior to measurements.  Pulse rate (bpm) will be 
counted over 60 seconds.  Blood pressure (mmHg) will be measured with a sphygmomanometer. 
Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, respiratory 
rate and temperature. 
8.2.3 
Clinical Laboratory Assessments 
Hematology, clinical chemistry, urinalysis and additional parameters to be tested are listed below: 
Hematology 
Platelet Count  
RBC Indices: 
Automated WBC Differential: 
RBC Count 
MCV 
Neutrophils 
WBC Count (absolute)  
MCH 
Lymphocytes 
Reticulocyte Count 
MCHC 
Monocytes 
Hemoglobin 
 
Eosinophils 
Hematocrit 
 
Basophils 
 
Clinical Chemistry 
BUN 
Chloride 
Alkaline phosphatase 
 
Creatinine 
AST (SGOT) 
Total and direct bilirubin 
 
Sodium 
ALT (SGPT) 
 
 
Potassium 
GGT 
 
 
 
Routine Urinalysis 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is abnormal) 
 
Other screening tests 
Urine Pregnancy Test (females of childbearing potential* only, using UPT tests provided by the 
Sponsor.) 
* Females of childbearing potential for this study includes any female 18 years of age or older who has not 
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation (at least six months prior 
to baseline) or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea greater than 12 
consecutive months in women 55 years or older). 
All results will be reported and must be reviewed by the investigator or designee. Abnormal results 
shall be assessed for clinical significance. Repeat lab testing may be requested at the discretion of 
the investigator.  If an AE should require laboratory testing, the results of the test should be 
obtained by the investigative site and filed in the subject’s documentation.  
8.2.4 
Adverse Events  
Adverse events (See section 9) will be collected for all untoward medical occurrences in a subject 
entered into this clinical trial (e.g. signed consent) whether or not a pharmaceutical product has 
been administered. Any event, including local tolerability assessments (see Section 8.2.6) that 

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requires specific treatment, results in interruption of treatment, or results in discontinuation of the 
subject from the study will also be reported as Adverse Events.   
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-
leading verbal questioning of the subject is the preferred method to inquire about AE occurrence.   
Appropriate questions include: 
x “How are you feeling?”  
x “Have you had any (other) medical problems since your last visit/contact?” 
x “Have you taken any new medicines, other than those provided in this study, since your last 
visit/contact?” 
8.2.5 
Subject Assessments 
Subjects must complete ALL self-assessments while at the clinic (e.g. HDSS, HDSM-Ax, DLQI) 
prior to assessments being made by the Investigator.  Please see Appendices 2, 3, and 4 for a full 
description of these assessments.   
8.2.6 
Local Tolerability Assessments 
Local tolerability assessments (See Appendix 5) will be evaluated through assessment of selected 
local signs and symptoms at the drug-application site. Burning, itching, dryness, scaling and 
erythema will be assessed using standardized 5-point scales (0-Absent to 4-Severe). These 
assessments are to be performed for both axillae individually. Subject assessments (burning and 
itching) will be made prior to the Investigator assessments (dryness, scaling and erythema).  
Subject Local Tolerability Assessments: Burning and itching for each axilla will be reviewed 
with the subject and assessed for the previous 24 hours using the standardized scales.   
Investigator Local Tolerability Assessments: Dryness, scaling and erythema for each axilla will 
be assessed by the investigator using the standardized scales. 
Local tolerability signs and symptoms that result in the subject’s requiring a concomitant therapy, 
interruption of treatment, or discontinuation from the study, will be reported as an AE.  
8.3 
Summary of Methods of Data Collection 
This protocol will utilize validated 21CFR Part 11 compliant electronic data capture (EDC) 
software to collect CRF data. The investigator must ensure that data are properly recorded on each 
subject’s eCRFs and related documents. When changes or corrections are made in the eCRF, the 
EDC system will maintain an audit trail of the person making the changes, the date and time of the 
change and the reason for the change. Only individuals listed on the Delegation of Responsibilities 
Log with responsibility for eCRF completion may make entries in the eCRFs. 
The investigator or physician sub-investigator must electronically sign and date each subject’s 
eCRF. Individuals who will be providing electronic signatures must first submit documentation 
with a handwritten signature acknowledging that their electronic signature is a legally binding 
equivalent to their handwritten signature. 

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9 
ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) 
9.1 
Safety Assessments 
Throughout the study, subjects will be monitored for signs and symptoms of AEs.  An AE can be 
any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not considered related to the medicinal (investigational) product.  This definition 
includes the worsening of a pre-existing condition, the development of investigational product 
dependency, and suspected investigational product-drug interactions. 
Adverse events will be collected for all untoward medical occurrences in a subject entered into this 
clinical trial (as defined by the study protocol) whether or not a pharmaceutical product has been 
administered. 
An SAE is an AE that meets one or more of the following criteria: 
x Results in death (including reports of death with no specific AE identified, i.e., “death only” 
reports) 
x Results in a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
x Is life-threatening 
x Requires inpatient hospitalization or prolongation of existing hospitalization 
x Results in persistent or significant disability/incapacity 
x Is a congenital anomaly/birth defect 
x Is an important medical event that may not fall into one of the above categories but may 
jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes above 
An Unexpected AE is any treatment-related AE that is not identified in nature, severity, or 
frequency in current literature on the test product (i.e., Investigators Brochure). 
9.1.1 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-
leading verbal questioning of the subject is the preferred method to inquire about AE occurrence.   
Appropriate questions include: 
x “How are you feeling?”  
x “Have you had any (other) medical problems since your last visit/contact?” 
x “Have you taken any new medicines, other than those provided in this study, since your last 
visit/contact?” 

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9.2 
Reporting Requirements 
9.2.1 
Serious and/or Unexpected Adverse Events 
Any serious or investigational product-related unexpected AE occurring in this study must 
be reported to the Medical Monitor/Brickell Biotech immediately upon awareness of the 
event per the following: 
A SAE form must be completed by the investigator and faxed to 973-331-1622 or email at 
wcunningham@cu-tech.com. At the time of the initial report the following information should be 
provided at a minimum: subject identifiers, adverse event description, event status and severity, 
onset date, date the Investigator learned of the event, criteria for classification of the event as 
serious, disposition of the subject and Investigator assessment of the association between the event 
and study drug. 
The investigator will keep the original of this SAE form on file at the study site. When the 
Investigator becomes aware of significant new information regarding an ongoing serious adverse 
event, a follow-up report should be promptly faxed to 973-331-1622 or email at 
wcunningham@cu-tech.com. When the investigator determines that there is no more information 
likely to be available, a final report should be provided. 
9.2.2 
Adverse Event Reporting 
All AEs, including SAEs and treatment-related unexpected AEs, must be recorded by the 
investigator on the standard AE form. The investigator will be required to describe the AE, onset 
and stop date, severity, the course of action taken, if any, relationship to the study drug as well as 
any pertinent data necessary to allow a complete evaluation of the AE. For SAEs, an additional 
report must be completed (this form will be provided in the Investigator Site Binder). 
A clinical determination of the intensity of an AE will be completed using the following 
definitions as guidelines: 
Mild: 
Awareness of sign or symptom, but easily tolerated 
Moderate: 
Discomfort enough to cause interference with usual activity 
Severe: 
Incapacitating with inability to work or do usual activity 

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The investigator must determine the relationship of the AE to the test article according to the 
following categories: 
Definitely 
Related 
An event that follows a reasonable temporal sequence from administration of the test 
article; that follows a known or expected response pattern to the test article; and that is 
confirmed by improvement on stopping or reducing the dosage, and reappearance of the 
event on repeated exposure (re-challenge). 
Probably 
Related 
An event that follows a reasonable temporal sequence from administration of the test 
article; that follows a known or expected response pattern to the test article; and that is 
confirmed by improvement on stopping or reducing the dosage of the test article; and that 
is unlikely to have been caused by concurrent/underlying illness or other drugs, 
procedures, or other causes. 
Possibly 
Related 
An event that follows a reasonable temporal sequence from administration of the test 
article; that follows a known or expected response pattern to the test article; but may have 
been caused by concurrent/underlying illness, other drug, procedure, or other causes. 
Unlikely 
Related 
An event that does not follow a reasonable temporal sequence from administration of the 
test article; that does not follow a known or expected response pattern to the test article, or 
most likely was caused by concurrent/underlying illness, other drug, procedure, or other 
causes, because of their known effects. 
Not 
Related 
An event almost certainly caused by concurrent/underlying illness, other drug, procedure, 
or other causes. 
9.2.3 
Pregnancy 
Sexually active females of childbearing potential (FOCBP)* must have a negative pregnancy test 
prior to study enrollment and must use an effective method of contraception during the course of 
the study, in a manner such that risk of failure is minimized.  Prior to study enrollment, FOCBP 
must be advised of the importance of avoiding pregnancy during trial participation and the 
potential risk factors for an unintentional pregnancy. The subject must sign an informed consent 
form documenting this discussion. 
FOCBP must agree to periodic pregnancy testing and use a medically acceptable method of 
contraception while receiving protocol-assigned product. This includes perimenopausal women 
who are less than 12 months from their last menses. Acceptable contraceptive methods include the 
following:  
x Abstinence for the duration of the study or where partner is sterile (e.g., vasectomy) is 
acceptable form of contraception 
x Hormonal contraception, including oral, injectable, or implantable methods started at 
least 2 months prior to screening, OR 
x Two forms of non-hormonal contraception, including intrauterine devices (at least 1-
week status post placement), or properly used barrier methods (e.g., male or female 
condoms, cervical cap/diaphragm, spermicidal agents, etc.). 
* Females of childbearing potential for this study includes any female 18 years of age or older who 
has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation (at least 

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six months prior to baseline) or bilateral oophorectomy) or is not postmenopausal (defined as 
amenorrhea greater than 12 consecutive months in women 55 years or older).   
Subjects who become sexually active or begin to have relations with a partner who is not sterile 
during the trial must agree to use an effective form of birth control for the duration of the study. 
9.2.3.1 
Time period for collecting pregnancy information 
FOCBP should be instructed to contact the investigator immediately if they suspect they might be 
pregnant (e.g., missed or late menstrual period).  If a subject or investigator suspects that a subject 
may be pregnant at any time during the study the investigational product must be withheld until the 
results of laboratory pregnancy testing are available.  If pregnancy is confirmed, the subject must 
not receive or apply further investigational product and must be discontinued from the study. 
9.2.3.2 
Action to be taken if pregnancy occurs 
If following initiation of investigational product, it is subsequently discovered that a trial subject 
was pregnant or may have been pregnant at the time of test article exposure, the investigator must 
immediately notify the Medical Monitor of this event, and record the pregnancy on the appropriate 
pregnancy surveillance form.  The form will be sent to the Medical Monitor by fax or email as 
listed on the title page of the protocol.  The investigator must notify the IRB of any pregnancy 
associated with the study therapy and keep careful source documentation of the event. 
Protocol-required procedures for those subjects that are discontinued from the study must be 
performed on the subject unless contraindicated by pregnancy (e.g., x-ray studies). Other 
appropriate pregnancy follow-up procedures should be considered if indicated, including 
counseling of the subject by the investigator and her managing physician or health care provider 
(e.g., obstetrician).  In addition, the investigator must report to the Medical Monitor, on the 
appropriate pregnancy surveillance form(s), any follow-up information regarding the course of the 
pregnancy, including perinatal (period immediately before and after birth) and neonatal (infants up 
to 28 days after birth) outcome.   
Although pregnancy itself is not an AE, any complications during pregnancy should be recorded as 
AEs (or SAEs – if they fulfill the SAE criteria).  Offspring will be followed for a minimum of 
eight weeks.  Any congenital anomaly/birth defect in a child born to a subject exposed to the test 
article(s) will be recorded as a SAE and details documented in the pregnancy surveillance form.  
An abortion, whether accidental, therapeutic or spontaneous will be reported as a SAE. 
9.2.4 
Follow-up and Final Reports 
Subjects who have had a SAE must be followed clinically until all parameters, including 
laboratory values, have either returned to normal or are otherwise explained. If death was the 
outcome of the event on the initial SAE Report, a Follow-up/Final Report, including autopsy 
report, when performed, must be completed. 
Subjects who report a pregnancy during the treatment phase of the study will be followed until 
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9.3 
Procedures for Unblinding of Investigational Product 
The sponsor will break the blind for subjects only if the medical monitor in conjunction with the 
Sponsor deems that a conclusion regarding the progression of the study, as planned, cannot be 
made based on the blinded data.  
In addition, when necessary for the safety and proper treatment of a subject, the investigator may 
unmask the subject’s investigational product assignment to determine and institute appropriate 
care, and subsequently the subject will be discontinued from receiving treatment. When possible, 
the Sponsor should be notified prior to unmasking. To break blind, the investigator or a designee 
will scratch off the blind break area (see Section 5.1) on the label panel adhered to the subject 
record at the time of dispensing the investigational product. In the event of a premature breaking of 
the randomization code, the reason for breaking the code will be recorded in the subject’s source 
documents. 
10 
STATISTICAL PROCEDURES 
A detailed statistical analysis plan will be generated prior to the final database lock. Database lock 
will precede unblinding and follow completion of data entry, verification and validation, database 
audit, and data clarification resolution. 
10.1 
Analysis Populations 
Subjects will be classified into the Safety, Intent-to-Treat (ITT), and Per-Protocol (PP) patient sets 
according to the following definitions. 
Safety Patient Set 
The Safety Patient Set will include all subjects randomized in the study who received study drug at 
least once.  Subjects will be included in the treatment group based on the majority of actual treatment 
they received (even if not the treatment group to which they were randomized).  
ITT Population 
The ITT Patient Set will include all subjects who were randomized and dispensed study drug.  
Subjects will be included in the treatment group to which they were randomized, regardless of the 
treatment received. 
PP Population 
The PP Patient Set will be a subset of the ITT Patient Set and will include subjects who meet the 
following criteria: 
x Meets the inclusion/exclusion criteria 
x Has not taken or applied any interfering concomitant medications. 
x Completed the following visits: 
o Visit 2 GSP 1, and the required GSP data collection 
o Visit 3 GSP 2, and the required GSP data collection 
o Visit 4 Re-screening GSP 3, and the required GSP data collection 
o Visit 11(GSP 4) Day 41 (± 2 days), and the required GSP data collection 
o Visit 12 (GSP 5) Day 42 (± 2 days), and the required GSP data collection 

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o Visit 13 (GSP 6) Day 43 (± 2 days), and the required GSP data collection 
Subjects will be included in the treatment group based on the treatment received. 
10.2 
Endpoints 
Generally, for statistical calculation of end of therapy change from baseline, baseline and end of 
therapy values are defined as follows. 
HDSM-Ax and HDSS:  
baseline value = average of two screening values, i.e. Visit 1 and Visit 4 
end of therapy value = average of Days 41, 42, and 43 measurements, i.e. Visit 11, Visit 12, and 
Visit 13, respectively. 
Gravimetric Sweat Production (both axilla combined):  
baseline value = the median of GSP1, GSP2, and GSP3 measurements obtained on Visit 2, Visit 3, 
and Visit 4, respectively 
end of therapy value = the median of GSP4, GSP5, and GSP6 measurements obtained on Visit 11, 
Visit 12, and Visit 13, respectively. 
Primary efficacy endpoint will be defined as: 
1. The proportion of subjects achieving at least a 1-point improvement in HDSM-Ax from 
baseline to end of therapy. 
2. Change of HDSM-Ax from baseline to end of therapy as a continuous measure 
Secondary efficacy endpoints will include the following.   
1. The proportion of subjects achieving at least a 2-point improvement in HDSM-Ax from 
baseline to end of therapy. 
2. The proportion of subjects achieving at least a 50% reduction in gravimetrically measured 
sweat production (both axilla combined) from baseline to end of therapy.  
3. The absolute change from baseline in gravimetrically measured sweat production to end of 
therapy. 
4. The percent change from baseline in gravimetrically measured sweat production to end of 
therapy. 
5. The proportion of subjects achieving at least a 1-point improvement in the HDSM-Ax score 
and at least 50% reduction in gravimetrically measured sweat production from baseline to end 
of therapy. 
6. The proportion of subjects achieving at least a 2-point improvement in the HDSM-Ax total 
score and at least 50% reduction in gravimetrically measured sweat production from baseline 
to end of therapy. 
7. The proportion of subjects achieving at least a 2-point improvement in HDSS from baseline to 
end of therapy. 

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8. The proportion of subjects achieving at least a 1-point improvement in HDSS from baseline to 
end of therapy. 
Other efficacy endpoints will include: 
1. The proportion of subjects achieving at least a 1-point improvement in the HDSM-Ax score 
from baseline to Days 8, 15, 22, 29, 36, 41, 42, 43, and 57. 
2. Change in HDSM-Ax from baseline to Days 8, 15, 22, 29, 36, 41, 42, 43, and 57 as a 
continuous measure 
3. The proportion of subjects achieving at least a 2-point improvement in the HDSM-Ax score 
from baseline to Days 8, 15, 22, 29, 36, 41, 42, 43, and 57. 
4. The proportion of subjects achieving at least a 50% reduction in gravimetrically measured 
sweat production (both axilla combined) from baseline to Days 8, 15, 22, 29, 36, 41, 42, 43, 
and 57. 
5. Percent change from baseline in gravimetrically measured sweat production at Days 8, 15, 22, 
29, 36, 41, 42, 43, and 57. 
6. Absolute change from baseline in gravimetrically measured sweat production at Days 8, 15, 
22, 29, 36, 41, 42, 43, and 57. 
7. The proportion of subjects achieving at least a 1-point improvement in the HDSM-Ax score 
and at least 50% reduction in gravimetrically measured sweat production from baseline to Days 
8, 15, 22, 29, 36, 41, 42, 43, and 57. 
8. The proportion of subjects achieving at least a 2-point improvement in the HDSM-Ax total 
score and at least 50% reduction in gravimetrically measured sweat production from baseline 
to Days 8, 15, 22, 29, 36, 41, 42, 43, and 57. 
9. The proportion of subjects achieving at least a 2-point improvement in HDSS from baseline to 
Days 8, 15, 22, 29, 36, 41, 42, 43, and 57. 
10. The proportion of subjects achieving at least a 1-point improvement in the HDSS on Days 8, 
15, 22, 29, 36, 41, 42, 43, and 57.   
11. Change in the modified dermatology life quality index (modified DLQI) from baseline to Day 
43 (end of therapy), and Day 57. 
10.3 
Efficacy Analyses 
Descriptive summaries will be provided for all efficacy endpoints by treatment groups at specified 
time points. Mean, standard deviation, median, minimum and maximum will be reported for 
continuous variables. Frequencies and proportions will be reported for categorical variables.  For 
continuous endpoints specified in 10.2, change from baseline will be similarly summarized.  
Primary Efficacy Analyses 
The mean of the items in sections No. 1, 2, and 3 of the HDSM-Ax (11 sub-items in total) will be 
used for analysis.  The mean will be derived by taking the total score and dividing by the number 
of questions answered. Subjects must answer at least 6 of the 11 sub-items to be evaluable for 
HDSM-Ax total score.  

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Change from baseline to end of therapy for the primary efficacy measure of HDSM-Ax will be 
analyzed both as a continuous measure and as a binary endpoint.  As a continuous measure, the 
HDSM-Ax change scores will be compared between all active treatment groups and the vehicle 
group by an ANCOVA model adjusting for the baseline HDSM-Ax score. As a binary measure, 
i.e. achieving a 1-point improvement or not from baseline to end of therapy, a logistic regression 
will be performed with treatment assignment and baseline HDSM-Ax score as independent 
variables in the model.  As a phase 2 study, a 1-sided p<0.10 in favor of an active treatment will be 
regarded as a positive sign for further investigation. 
Missing data will not be imputed for the primary analyses.  As sensitivity analyses, mixed model 
repeated measures (MMRM) analyses may be performed using all available HDSM-Ax change 
from baseline data on study days 8, 15, 22, 29, 36, and end of therapy.   
Additional Efficacy Analyses 
Analyses for secondary and other efficacy endpoints will be similar to the binary HDSM-Ax 
analysis described above.  For gravimetric results analyzed as continuous measures, analyses 
assuming Normality for the data distribution (i.e. comparing means) and analyses using rank 
transformed data (i.e. comparing medians) will both be performed.  All non-primary analyses will 
be based on available data only.  
In parallel to the traditional statistical analysis, psychometric evaluation of the HDSM-Ax will be 
carried out to confirm the most appropriate HDSM-Ax scoring algorithm and to examine internal 
validity, construct validity (i.e., examinations of the magnitude of correlation between the HDSM-
Ax total score (Items 1, 2, and 3) and key variables such as; items 4 and 5 of the HDSM-Ax, 
HDSS and gravimetrically measured sweat production), stability, reliability, ability to detect 
change, and interpretability of clinical trial results. 
10.4 
Safety Analyses 
Safety variables are AEs, blood laboratory evaluations, UPTs (as required), local tolerability 
assessments and vital signs. 
Adverse events will be coded from the verbatim text into preferred term (PT) and primary system 
organ class (SOC) using the most current version of Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment-emergent AEs will be summarized in the following tables: all reported 
AEs, all treatment-related AEs, all SAEs, and AEs leading to investigational product 
discontinuation. The number and percent of subjects reporting the AE at least once will be 
tabulated according to the highest severity reported.  
Laboratory evaluations and UPTs parameters will be summarized.  
Vital signs, including changes from baseline, will be summarized by descriptive statistical methods 
as previously described.  
Local tolerability assessments will also be summarized similarly as the treatment related AEs.  
10.5 
Sample Size and Power Estimation 
For the binary version of the primary endpoint, i.e. proportion of subjects achieving at least a 1-
point improvement in HDSM-Ax from baseline to end of therapy, assume the true response rates 

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to be 75% for each BBI-4000 arm and 50% for vehicle control (based on prior data).  With 100 
evaluable subjects at a 1:1 ratio for each pairwise comparison between a BBI-4000 arm and the 
vehicle arm, i.e. 50 evaluable subjects per arm, the power is approximately 0.87 for observing a 
response rate difference in favor of BBI-4000 at a 1-sided p<0.10 level.  To limit the study-wide 
false positive rate to 0.10, a gate-keeping hierarchical testing algorithm will be employed.  That is, 
the BBI-4000 15% group will be compared to the vehicle first, if the result is favorable with a 1-
sided p<0.10, then the BBI-4000 10% group will be compared to vehicle.  Similarly, if the BBI-
4000 10 % is favorable with a 1-sided p<0.10, then the BBI-4000 5% group will be compared to 
vehicle. 
For the continuous version of HDSM-Ax change from baseline to end of therapy, assume the true 
mean difference between each BBI-4000 arm and the vehicle arm to be 0.18, with a common 
standard deviation of 0.36, i.e. an effect size (mean difference/standard deviation) of 0.50.  With 
100 evaluable subjects at a 1:1 ratio for each pairwise comparison between a BBI-4000 arm and 
the vehicle arm, the power is approximately 0.89 for observing a difference in favor of BBI-4000 
at a 1-sided p<0.10 level.  Same as for the binary version of HDSM-Ax, the gate keeping 
hierarchical testing algorithm will be employed for the continuous data.  
Assuming an approximate 10% non-evaluable rate for the ITT primary efficacy analyses, 220 
randomized subjects are targeted for enrollment. 
 
11 
STUDY ADMINISTRATION PROCEDURES 
11.1 
Subject Entry Procedures 
11.1.1 
Overview of Entry Procedures 
Subjects with hyperhidrosis as defined by the criteria Sections 4.2  and 4.3 (inclusion/exclusion 
criteria) will be considered for entry into this study. 
11.1.2 
Informed Consent and Subject Privacy 
The study will be discussed with the subject, and a subject wishing to participate must give 
informed consent prior to any study-related procedures or change in treatment. The subject must 
also give Authorization for Use and Release of Health and Research Study Information and other 
written documentation in accordance with the relevant country and local privacy requirements 
(where applicable) prior to any study-related procedures or change in treatment.  
11.1.3 
Method for Assignment to Study Product Groups 
All subjects who have signed an ICF will receive a 5-digit subject number, this number will be 
composed of a 2-digit site number followed by a 3-digit sequentially assigned number stating at 
001, at each site. For instance, the first subject from site 01 will have 01001 as their assigned 
subject number; the subsequent subject from this site will have 01002 as their assigned subject 
number. The first subject from site 02 will have 02001 as their assigned subject number; the 
subsequent subject from this site will have 02002 as their assigned subject number. This number 

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22 February 2017 
will be unique to each subject and will be used to identify the subject throughout the study. This 
number is different from the randomization/kit number. 
When subjects qualify for the study (determined by the investigator at the Rescreening Visit), they 
will be randomized to investigational product groups and will receive a randomization number. 
The kit carton and treatment plastic pumps have the randomization numbers displayed in their 
label.  
The next eligible subject will be assigned the lowest available randomization number from the 
treatment kits available at the depot. In this manner, eligible subjects will be randomized to the 
investigational product sequence in accordance with the randomization schedule. The investigator 
will document the randomization/kit numbers in the source and on the CRF. The tear-off portion of 
the carton label from the outer carton (with blind-break panel) will be removed along the label 
perforation and placed into the study subject source file. In the event a subject is randomized at the 
Rescreening Visit but is not dispensed study medication (e.g. deemed ineligible at Baseline, 
withdraws consent, etc.) the randomization number will not be reassigned; the subject will be 
considered an early termination and the kit shall be placed in quarantine in the site’s inventory.  
Subjects will be randomized to receive BBI-4000 5%, or 10%, or, 15% gel, or vehicle (placebo) 
gel in a balanced ratio of 1:1:1:1. 
11.2 
Compliance with Protocol 
At each post-baseline visit, the following activities will occur to ensure compliance with the 
protocol: 
x Subjects will be asked if they have used the investigational product as instructed. 
x Subjects will be asked if they experienced any problems dispensing the investigational 
product. 
x Subjects will be asked if they used any products on their axillae (including 
antiperspirant/deodorant). 
x Site staff will review concomitant medication use since the previous visit and determine if 
any concomitant medication use qualifies as a protocol deviation  
x At Day 22 (Visit 8) and the End of Treatment Visit site staff will collect the dispensing 
container from the subject and record the weight of the container. 
11.3 
Study Termination 
The study may be stopped at a study site at any time by the site investigator, after first notifying 
the Sponsor and discussing the reason(s) for stopping the study.  Brickell Biotech may stop the 
study with appropriate notification.  

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12 
ADMINISTRATIVE ISSUES 
12.1 
Posting of Information on Clinicaltrials.gov 
Study information from this protocol will be posted on clinicaltrials.gov before enrollment of 
subjects begins. 
12.2 
Protection of Human Subjects 
12.2.1 
Compliance with Informed Consent Regulations (US 21 CFR Part 50) 
and Relevant Country Regulations 
Written informed consent is to be obtained from each subject prior to enrollment into the study.  
Subjects may be consented up to 56 days before baseline visit. 
12.2.2 
Compliance with IRB Regulations 
This study is to be conducted in accordance with IRB regulations (US 21 CFR Part 56.103). The 
investigator must obtain approval from a properly constituted IRB prior to initiating the study and 
re-approval or review at least annually. Brickell Biotech is to be notified immediately if the 
responsible IRB has been disqualified or if proceedings leading to disqualification have begun. 
Copies of all IRB correspondence with the investigator will be provided to Brickell Biotech. 
12.2.3 
Compliance with Good Clinical Practice 
This protocol is to be conducted in accordance with the applicable Good Clinical Practice (GCP) 
regulations and guidelines, e.g., the International Conference on Harmonisation (ICH) Guideline 
on GCP. 
12.3 
Changes to the Protocol 
The investigator should not implement any deviation from or changes to the protocol without 
approval by Brickell Biotech and prior review and documented approval/favorable opinion from 
the IRB of a protocol amendment, except where necessary to eliminate immediate hazards to study 
subjects, or when the changes involve only logistical or administrative aspects of the study (e.g., 
change in monitors, change of telephone numbers). 
12.4 
Subject Confidentiality 
A report of the results of this study may be published or sent to the appropriate health authorities in 
any country in which the investigational product may ultimately be marketed, but a subject’s name 
will not be disclosed in these documents. A subject's name may be disclosed to the Sponsor of the 
study, Brickell Biotech, the governing health authorities, or the FDA if they inspect the study 
records. Appropriate precautions will be taken to maintain confidentiality of medical records and 
personal information. 

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12.4.1 
Subject Privacy 
Written Authorization and other documentation in accordance with the relevant country and local 
privacy requirements (where applicable) is to be obtained from each subject prior to enrollment 
into the study, in accordance with the applicable privacy requirements (e.g., the Health Insurance 
Portability and Accountability Act Standards for Privacy of Individually Identifiable Health 
Information; HIPAA). 
12.5 
Documentation 
12.5.1 
Source Documents 
Source documents may include a subject's medical records, hospital charts, clinic charts, the 
investigator's subject study files, as well as the results of diagnostic tests. The investigator's copy 
of the CRF serves as part of the investigator's record of a subject's study-related data.  
12.5.2 
Electronic Case Report Form Completion 
The investigator is responsible for ensuring that data are properly recorded on each subject's 
eCRFs and related documents. The eCRFs are to be completed in a timely manner as defined in the 
clinical study agreement, or as otherwise specified by Brickell Biotech. 
12.5.3 
Retention of Documentation 
All study related correspondence, subject records, consent forms, subject privacy documentation, 
records of the distribution and use of all investigational products, and copies of CRFs should be 
maintained on file. 
The Sponsor-specific essential documents should be retained until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirement(s) or if needed by the Sponsor. 
Brickell Biotech requires that it be notified in writing if the investigator wishes to relinquish 
ownership of the data so that mutually agreed-upon arrangements can be made for transfer of 
ownership to a suitably qualified, responsible person. 
12.6 
Labelling, Packaging, Storage, and Return or Disposal of 
Investigational Product 
12.6.1 
Labeling/Packaging 
The investigational product will be packaged, labeled, and supplied by Brickell Biotech. The 
product will be identified as an investigational compound, for external use. The study number and 
randomization number will be identified on the unit label of the product.  

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22 February 2017 
12.6.2 
Storage of Investigational Product  
The investigational product must be stored in a secure area with access limited to the investigator 
and authorized site staff and administered only to subjects entered into the clinical study, at no cost 
to the subject, in accordance with the conditions specified in this protocol. 
Investigational product should be stored at controlled room temperature 68oF to 77oF (20oC to 
25oC) with excursion permitted between 59°F to 86°F (15oC to 30oC). Maintenance of a 
temperature log (manual or automated) is required.   
12.6.3 
Clinical Supply Inventory 
The investigational product must be dispensed only by an appropriately qualified person to 
subjects in the study.  The investigational product is to be used in accordance with the protocol by 
subjects who are under the direct supervision of the principal investigator. 
The investigator or designated site staff are responsible for investigational product accountability, 
reconciliation, and record maintenance.  The investigator or designated site staff must maintain 
investigational product accountability records throughout the course of the study.  Discrepancies 
are to be reconciled or resolved and documented.   
12.6.4 
Return or Disposal of Investigational Product 
All investigational product (used and unused) will be returned to Brickell Biotech or its designee 
for destruction.  
12.7 
Monitoring by the Sponsor 
A representative of the Sponsor will monitor the study on a periodic basis. The determination of 
the extent and nature of monitoring will be based on considerations such as the objective, purpose, 
design, complexity, blinding, size, and endpoints of the study.  
Authorized representatives of Brickell Biotech and/or regulatory authority representatives will 
conduct on-site visits to review, audit, and copy study-related documents. These representatives 
will meet with the investigator(s) and appropriate staff at mutually convenient times to discuss 
study-related data and questions. 
12.8 
Publications 
Brickell Biotech as the sponsor has proprietary interest in this study. Authorship and manuscript 
composition will reflect joint cooperation between the investigator and Brickell Biotech personnel. 
Authorship will be established prior to the writing of the manuscript. No manuscripts regarding 
this study will be submitted without written authorization from Brickell Biotech. 

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13 
REFERENCES 
1. Doolittle J, Walker P, Mills T, Thurston J.  Hyperhidrosis: an update on prevalence and 
severity in the United States.  Arch Dermatol Res. 2016; 308(10):743-749. 
 

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14 
APPENDICES 
APPENDIX 1:  GRAVIMETRICALLY MEASURED SWEAT 
PRODUCTION 
Method: Axilla Filter Paper Gravimetric Sweat Production Measurements 
Set Up 
IMPORTANT:  Make sure that you distinguish each gravimetric collection packet Right (R) from 
Left (L) throughout the gravimetric measurement (i.e., during set up, measurement). 
x 
Clip or shave axilla hair if present.  Use an electric razor or clippers so a short stubble (<1mm) 
is present (blade shaving may irritate the skin or cause folliculitis; ok for men and women who 
uses a manual razor routinely). Wash and clean the axilla to remove all loose hair or stubble.   
Towel dry the axilla(s). 
x 
Place the subject in a room with controlled humidity and temperature between 20°C and 25°C 
(68°F to 77°F) for at least 30 min.   During acclimation the subject should remain in a semi-
recumbent position.  
x 
Measurements will be done in the same room throughout the study. 
x 
The same Study Site Staff member will perform the evaluation for each subject both within 
and across subjects.  In the event that this is not possible, given extenuating circumstances 
(e.g. vacation, illness, etc.), another qualified Study Site Staff Member cross trained by the 
originally assigned staff member may perform these activities.  
x 
Refer to detailed study training manual and video for step-by-step directions.  
Filter Paper Measurement 
x 
Prepare the cotton towel, filter paper and container for the assessment.   
x 
Place one filter paper and the weight container with lid on a balance sensitive to 1 mg and 
record its weight.  Tare the weight of the filter paper and weigh container.  
x 
Have subject semi-reclining position with the axilla fully exposed and the arm resting 
comfortably above the head.   
x 
Dry the axilla gently with the cotton towel. 
x 
Using talc free gloves, place the pre-weighed filter paper in the center of the axilla, against the 
subject’s skin, have the patient carefully fold their axilla down to hold the filter paper in place.  
Immediately start the timer for 5 min.  After 5 minutes ask the patient to lift his/her arm and 
gently lift the filter paper out of the axillary vault and place it into the weight container and 
replace lid to avoid evaporative loss of fluid.   
x 
Record the weight.  
x 
Refer to detailed study training manual and video for step-by-step directions.  

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APPENDIX 2:  HYPERHIDROSIS DISEASE SEVERITY SCALE 
(HDSS) 
 
How would you rate the severity of your axillary hyperhidrosis? 
☐ 
My sweating is never noticeable and never interferes with my 
daily activities 
Score 1 
☐ 
My sweating is tolerable but sometimes interferes with my 
daily activities 
Score 2 
☐ 
My sweating is barely tolerable and frequently interferes with 
my daily activities 
Score 3 
☐ 
My sweating is intolerable and always interferes with my daily 
activities 
Score 4 
 
 
 

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APPENDIX 3:  HYPERHIDROSIS DISEASE SEVERITY 
MEASURE-AXILLA (HDSM-AX) 
 

HDSM-Ax Version 1.1 
CONFIDENTIAL 
22 February 2017 
Hyperhidrosis Disease Severity Measure--Axillary 
(HDSM-Ax) 
 
INSTRUCTIONS:  We are interested in finding out about your current experience with excessive underarm 
sweating.   
x 
Please consider excessive sweating in your underarms only when selecting the answer to each 
question. 
x 
For each statement, please provide the response that best describes your experience since you woke 
up yesterday. 
x 
Please answer ALL questions even if some seem similar to others or seem irrelevant to you. 
_______________________________________________________________________________ 
1. Since you woke up yesterday, how often did you experience the following while you were awake?  
(Please select the number that best describes your experience.) 
 
None of 
the time  
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of 
the time 
a) Damp or wet clothing because of your 
underarm sweating? 
0 
1 
2 
3 
4 
b) Underarm sweating for no apparent reason? 
0 
1 
2 
3 
4 
 
2. Since you woke up yesterday, how severe was your experience with the following?  
(Please select the number that best describes your experience.) 
 
I did not 
experience 
this  
Mild 
Moderate Severe 
Very 
severe 
a) Underarm sweating when you felt 
nervous, stressed or anxious? 
0 
1 
2 
3 
4 
b) Damp or wet clothing because of your 
underarm sweating? 
0 
1 
2 
3 
4 
c) 
Underarm sweating after little or no 
physical exercise? 
0 
1 
2 
3 
4 
d) Underarm wetness? 
0 
1 
2 
3 
4 
e) Underarm sweating for no apparent 
reason? 
0 
1 
2 
3 
4 
f) 
Underarm sweating that was 
unmanageable? 
0 
1 
2 
3 
4 
g) Underarm sweating when you were 
cool? 
0 
1 
2 
3 
4 

HDSM-Ax Version 1.1 
CONFIDENTIAL 
22 February 2017 
 
3. Since you woke up yesterday, what was your experience with each of the following?  
(Please select the number that best describes your experience.) 
 
Not at all  
Slight  
Moderate Strong 
Very 
strong 
a) Feeling the need to change clothes because 
of underarm sweating? 
0 
1 
2 
3 
4 
b) Feeling the need to wipe sweat from your 
underarms? 
0 
1 
2 
3 
4 
 
SUMMARY QUESTIONS: 
4. Since you woke up yesterday, how much of the time did you experience excessive underarm sweating 
while you were awake? (Please select the number that best describes your experience.) 
0 
None of the time 
1 
A little of the time 
2 
Some of the time 
3 
Most of the time 
4 
All of the time 
 
5. How severe was your underarm sweating AT ITS WORST since you woke up yesterday?  
(Please select the number that best describes your experience.) 
0 
I did not have underarm sweating (i.e., completely dry) 
1 
I had underarm sweating but it was mild (i.e., moist) 
2 
I had underarm sweating and it was moderate (i.e., damp) 
3 
I had underarm sweating and it was severe (i.e., wet) 
4 
I had underarm sweating and it was very severe (i.e., soaking) 
 
6. How normal was your level of physical exercise and stress since you woke up yesterday?  
(Please select all that apply.) 
   
It was a normal day in terms of physical exercise or stress.  
   
I experienced more physical exercise than usual. 
   
I experienced more nervousness, stress, or anxiety than usual. 
   
I experienced less physical exercise than usual. 
   
I experienced less nervousness, stress, or anxiety than usual. 
 

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APPENDIX 4:  QUALITY OF LIFE ASSESSMENT 
DERMATOLOGY LIFE QUALITY INDEX-Axilla 
The aim of this questionnaire is to measure how much the SWEATING in your underarms has 
affected your life OVER THE LAST WEEK. 
Please tick one box for each question. 
DERMATOLOGY LIFE QUALITY INDEX-Axilla 
1. 
Over the last week, how itchy, sore, painful or 
stinging has your underarm skin been? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
 
 

2. 
Over the last week, how embarrassed or self-
conscious have you been because of your 
underarm sweating? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
 
 

3. 
Over the last week, how much has your underarm 
sweating interfered with you going shopping or 
looking after your home or garden?  
Very much 
 
A lot 

A little 

Not at all 

Not relevant 

 
 

4. 
Over the last week, how much has your underarm 
sweating influenced the clothes you wear? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
Not relevant 


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22 February 2017 
DERMATOLOGY LIFE QUALITY INDEX-Axilla 
5. 
Over the last week, how much has your underarm 
sweating affected any social or leisure activities? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
Not relevant 

 
 

6. 
Over the last week, how much has your underarm 
sweating made it difficult for you to do any sport? 
Very much 
 
A lot 
 
A little 
 
Not at all 

Not relevant 

 
 

7. 
Over the last week, has your underarm sweating 
prevented you from working or studying? 
Yes 
 
No 
 
Not relevant 
 
 
 

 
If "No", over the last week how much has your 
underarm sweating been a problem at work or 
studying? 
A lot 
 
A little 
 
Not at all 
 
 
 

8. 
Over the last week, how much has your underarm 
sweating created problems with your partner or 
any of your close friends or relatives? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
Not relevant 

 
 


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DERMATOLOGY LIFE QUALITY INDEX-Axilla 
9 
Over the last week, how much has your underarm 
sweating caused any sexual difficulties? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
Not relevant 

 
 

10. Over the last week, how much of a problem has the 
treatment for your underarm sweating been, for 
example by making your home messy, or by taking 
up time? 
Very much 
 
A lot 
 
A little 
 
Not at all 
 
Not relevant 

 
Please check that you have answered EVERY question.  Thank you. 
AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the authors. 
 
 
 

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APPENDIX 5:  TOLERABILITY ASSESSMENTS 
 
These assessments are to be performed for both axillae individually.  The designation of “Right 
Axilla” or “Left Axilla” in the source documents and e-CRFs refers to the subject’s right and left 
axilla respectively in all cases. Subject assessments are to be performed prior to investigator 
assessments. 
Local Tolerability (Subject):  The severity of burning and itching on the axilla as reported by the 
subject to the investigator: 
Score 
Burning 
Itching 
0 = Absent Normal, no discomfort 
Normal, no discomfort 
1 = Minimal An awareness, but no discomfort  
An awareness, but no discomfort  
2 = Mild Noticeable discomfort causing 
intermittent awareness 
Noticeable discomfort causing 
intermittent awareness 
3 = Moderate Noticeable discomfort causing 
continuous awareness 
Noticeable discomfort causing 
continuous awareness 
4 = Severe 
Definite discomfort causing 
continuous awareness, interfering 
occasionally with normal daily 
activities 
Definite discomfort causing 
continuous awareness, interfering 
occasionally with normal daily 
activities 
Local tolerability (Investigator):  The Investigator will grade the severity of dryness, scaling and 
erythema on the each axilla as observed: 
Score 
Dryness 
Scaling 
Erythema 
0 = Absent 
None 
No scaling 
No redness 
1 = Minimal 
Barely perceptible dryness by palpation 
with no accentuation of skin markings, 
skin desquamation (flakes), or fissure 
formation 
Fine scaling, 
barely 
perceptible 
Faint red or pink 
coloration, barely 
perceptible 
2 = Mild 
Easily perceptible dryness by palpation 
with accentuation of skin markings but 
no skin desquamation (flakes) or fissure 
formation 
Slight scaling, 
noticeable only 
with light 
scratching 
Light red or pink 
coloration 
3 = Moderate 
Easily noted dryness with accentuation 
of skin markings and skin desquamation 
(small flakes) but no fissure formation 
Definitely 
noticeable 
scaling 
Medium red 
coloration 
4 = Severe 
Easily noted dryness with accentuation 
of skin markings, skin desquamation 
(large flakes), and/or fissure formation 
Extensive 
scaling 
Beet red 
coloration 

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APPENDIX 6:  STUDY DRUG APPLICATION & SUBJECT 
INSTRUCTIONS 
 
Apply the investigational product every day, at night prior to bedtime as follows: 
1. Expose the underarm areas and ensure they are dry. Don’t wash the underarm areas prior to drying.  
2. Carefully, by slowly applying pressure to the actuator with an index finger, place the gel of ONE full 
actuation to the dome of the white plastic applicator (provided).  
3. Take the applicator introducing the three (3) middle fingers of the left hand in the plastic applicator hole 
and immediately apply study product to the right underarm area. 
4. Distribute the product in a way that covers all the underarm area where the hair grows by gently 
applying a layer of the product. 
5. Repeat the procedure to apply the study product to the left underarm. 
6. Wash both hands and the plastic applicator thoroughly for about 2 minutes. 
7. Allow the study product to dry for 5 minutes before putting any clothes on the upper body. 
Important information: 
x 
The subject should sleep in a T-shirt or similar pajama to avoid touching the underarm area while 
sleeping. 
x 
Subjects should maintain their underarm areas grooming habits but should not shower, shave, or wash 
the underarm area for at least 8 hours after study product application. If the subject takes shower, shave 
or wash the underarm area at night then it should be at least 30 mins before study product application. 
Ensure the underarm areas are dry. 
x 
Subjects should not apply any other product to the axillary area (including deodorant) for at least 8 
hours after study product application.  
x 
The subject should use the applicator provided to avoid contact with skin of the hands.  Special care 
should be taken to avoid contact of the gel with the eyes or mouth. Of note, hands should be washed 
after applying the gel to avoid possible skin and eye contact with the gel. 
x 
The study product contains alcohol and is flammable.  The subject should avoid fire, flame or smoking 
during the application and until the gel has dried.  The subject should not expose the container to fire, 
flame or extreme heat. 
On the day of all clinic study visits you may shower but are NOT permitted to: 
x 
Do Not apply any product to your axilla (including deodorant). 
x 
Exercise is to be avoided (e.g., gym, jogging, etc.). 
x 
Avoid caffeine and tea until the gravimetric assessments is completed  

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SUBJECT INSTRUCTIONS 
Please follow these instructions carefully.  If you do not understand anything in these instructions, 
ask the study doctor for help.  To contact the study staff, call the telephone number noted below if 
you have any questions: 
Contact: 
 
 
 
 
 
 
At: 
 
 
 
 
If you participate in this study, you will be expected to: 
x 
Follow the instructions you are given and come to the study center for all visits with the study doctor or 
study staff. 
x 
Tell the study doctor or study staff about any changes in your health or the way you feel. 
x 
Tell the study doctor or study staff if you want to stop being in the study at any time. 
x 
Do not shower, shave, or wash the underarm area for at least 8 hours after study product application. 
x 
Be careful not to touch your eyes or mouth with the gel or with your hands while applying the gel. 
x 
Use or practice the required method of birth control throughout the entire study if you are able to 
become pregnant. 
x 
Not breastfeed while you are in the study (for applicable females). 
x 
Use a T-shirt to sleep or similar pajama and avoid touching the underarm area. 
x 
Use only the non-antiperspirant deodorant provided to you. 
x 
Do not apply any other product to the axillary area (including deodorant) for at least 8 hours after study 
product application. 
x 
Not start any new medications or change your medications without approval from the study doctor. 
x 
Not allow access to the study medication assigned to you to anyone beside the study staff. 
x 
Store the study medications according to the instructions on the label. 
 
IMPORTANT:  
x 
The investigational product contains alcohol and is flammable.  
x 
Avoid fire, flame or smoking during the application and until the gel has dried.  
x 
Do Not expose the container to fire, flame or extreme heat. 
 
Bring your Study Drug container to the clinic for study Visit 8 (Day 22) and to the End of Treatment 
Visit on Day 43 (Visit 13)  

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APPENDIX 7:  EXAMPLE POTENT INHIBITORS OF CYP3A 
AND CYP2D6 
 
Example Potent Inhibitors of CYP3Aa 
apigenin 
hydroxyzine 
protease inhibitors 
antipsychotics 
interferon 
ritonavir 
candesartan 
isoniazid 
St. John’s Wortc  
(and other herbal 
supplements)b 
chloramphenicol 
itraconazole 
chlorpheniramine 
ketoconazole 
clarithromycin 
methoxsalen 
sulphaphenazole 
cobicistat 
mibefradil 
telithromycin 
cilexetil 
(cyclohexylcarbonate ester 
prodrug of candesartan) 
miconazole 
tripelennamine 
mifepristone 
valproic acid 
mometasone furoate  
voriconazole 
diphenhydramine 
montelukast 
zafirlukast 
felodipine  
nefazodone 
 
gestodene  
promethazine  
 
 
Example Potent Inhibitors of CYP2D6a 
bupropion 
fluoxetine 
paroxetine 
quinidine 
terbinafine 
 
a) Also refer to FDA reference link “Drug Development and Drug Interactions: Table of 
Substrates, Inhibitors and Inducers” 
[http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInt
eractionsLabeling/ucm093664.htm#table2-2] 
b) Prohibited medications (see section 6.2) 
c) Discontinue within 30 days of the baseline visit for hyperhidrosis.