Conditions: Hyperhidrosis
Keywords: sweat gland disease sweating underarm
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 227
Healthy volunteers: no

Brief summary:
This study is being conducted to assess the safety and efficacy of 3 concentrations of BBI-4000 and vehicle (4 treatment arms), applied for the treatment of axillary hyperhidrosis.

Detailed description:
This is a Multicenter, Randomized, Double Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of 3 concentrations of Topically Applied BBI-4000 in Subjects with Axillary Hyperhidrosis.

Safety will be assessed through collection of vital signs, adverse events, local skin responses, hematology, serum chemistry laboratory testing and urinalysis.

Arms:
arm 1: BBI-4000 gel, 5% applied once to each axilla daily arm 2: BBI-4000 gel, 10% applied once to each axilla daily arm 3: BBI-4000 gel, 15% applied once to each axilla daily arm 4: Placebo, applied once to each axilla daily

Interventions: intervention 1: BBI-4000 gel, 5% intervention 2: BBI-4000 gel, 10% intervention 3: BBI-4000 gel, 15% intervention 4: Vehicle (Placebo)
Intervention descriptions: intervention 1: BBI-4000 gel, 5% applied once to each axilla daily intervention 2: BBI-4000 gel, 10% applied once to each axilla daily intervention 3: BBI-4000 gel, 15% applied once to each axilla daily intervention 4: Placebo, applied once to each axilla daily

Protocol document:
Prot_000.pdf: 
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 
Page 4 of 65 
CONFIDENTIAL 
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 
 
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22 February 2017 
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 
Page 6 of 65 
CONFIDENTIAL 
22 February 2017 
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 
Page 7 of 65 
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22 February 2017 
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 
CONFIDENTIAL 
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 
CONFIDENTIAL 
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 
Page 11 of 65 
CONFIDENTIAL 
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 
CONFIDENTIAL 
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 
Page 15 of 65 
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. 
 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 25 of 65 
CONFIDENTIAL 
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 
CONFIDENTIAL 
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 
Page 27 of 65 
CONFIDENTIAL 
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. 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 28 of 65 
CONFIDENTIAL 
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.).   
 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 29 of 65 
CONFIDENTIAL 
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).   


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 31 of 65 
CONFIDENTIAL 
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. 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 32 of 65 
CONFIDENTIAL 
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). 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 33 of 65 
CONFIDENTIAL 
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. 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 34 of 65 
CONFIDENTIAL 
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. 


BBI-4000 Gel 
 
Protocol BBI-4000-CL-203 
Page 35 of 65 
CONFIDENTIAL 
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 
pregnancy resolution and information regarding the health status of the infant will be collected. 


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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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Protocol BBI-4000-CL-203 
Page 49 of 65 
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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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22 February 2017 
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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22 February 2017 
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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Protocol BBI-4000-CL-203 
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22 February 2017 
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. 

SAP_001.pdf: 
Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
Brickell Biotech, Inc. 
BBI-4000-CL-203 
 
 
 
 
Protocol 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 
Protocol Version 
and Date: 
Version/Amendment 1.0; 22 February 2017 
 
Sponsor: 
 
Brickell Biotech, Inc. 
5777 Central Ave., Suite 102 
Boulder, CO 80301 
Prepared By: 
Viv Goodell 
Agility Clinical, Inc. 
6005 Hidden Valley Road, Suite 170 
Carlsbad, CA 92011 
Document Version 
and Date: 
Version 2.0; 27 July 2017 
 
 
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NCT#
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Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
2 TABLE OF CONTENTS 
 
1 
Statistical Analysis Plan Approval ............................................................................2 
2 
Table of Contents ........................................................................................................3 
3 
List of Abbreviations ..................................................................................................6 
4 
Introduction .................................................................................................................8 
5 
Study Objectives .........................................................................................................8 
5.1 
Primary Study Objectives .....................................................................................8 
5.2 
Secondary Study Objective ...................................................................................8 
6 
Investigational Plan ....................................................................................................9 
6.1 
Overall Study Design .............................................................................................9 
6.2 
Schedule of Assessments ......................................................................................10 
6.3 
Treatments ............................................................................................................11 
6.3.1 
Treatments Administered .............................................................................11 
6.3.2 
Method of Assigning Subjects to Treatment Groups .................................11 
6.4 
Efficacy and Safety Variables .............................................................................11 
6.4.1 
Efficacy Variables ..........................................................................................11 
6.4.2 
Description of Safety Variables ....................................................................14 
6.5 
Data Quality Assurance .......................................................................................15 
7 
Statistical Methods ....................................................................................................16 
7.1 
General Methodology ..........................................................................................16 
7.1.1 
Reporting Conventions ..................................................................................16 
7.1.2 
Standard Calculations ...................................................................................17 
7.2 
Analysis Populations ............................................................................................18 
7.3 
Study Subjects ......................................................................................................19 
7.3.1 
Disposition of Subjects ...................................................................................19 
7.3.2 
Protocol Deviations ........................................................................................19 
7.4 
Efficacy..................................................................................................................19 
7.4.1 
Datasets Analyzed ..........................................................................................19 
7.4.2 
Demographic and Other Baseline Characteristics......................................19 
7.4.3 
Measurements of Treatment Compliance ...................................................20 
7.4.4 
Primary Efficacy Endpoint Analysis Methods ............................................20 
7.4.5 
Secondary and Other Efficacy Endpoint Analysis Methods......................22 
7.4.6 
Statistical/Analytical Issues ...........................................................................24 
7.5 
Safety Analysis .....................................................................................................25 
7.5.1 
Extent of Exposure .........................................................................................25 
7.5.2 
Adverse Events ...............................................................................................25 
7.5.3 
Local Tolerability Assessments .....................................................................26 
7.5.4 
Deaths, Other Serious Adverse Events, and Other Significant Adverse 
Events ..............................................................................................................26 
7.5.5 
Clinical Laboratory Evaluation ....................................................................27 
7.5.6 
Vital Signs, Physical Findings, and Other Observations Related to Safety27 
 
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7.6 
Determination of Sample Size .............................................................................28 
7.7 
Changes in the Conduct of the Study or Planned Analyses .............................29 
7.8 
Changes in SAP from Version 1.0 to Version 2.0..............................................29 
8 
Reference List ............................................................................................................29 
Appendix A: List of Tables, Figures and Data Listings ...............................................31 
Appendix B: Table Layouts ............................................................................................38 
Appendix C: Listing Layouts ..........................................................................................85 
 
 
 
 
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TABLE OF TABLES 
Table 1 
List of Abbreviations .................................................................................6 
Table 2 
Time and Events Table ............................................................................10 
Table 3 
Laboratory Tests ......................................................................................15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3 LIST OF ABBREVIATIONS  
Table 1 
List of Abbreviations  
 
Abbreviation 
Definition  
AE 
adverse event 
AIC  
Akaike information criterion 
ANCOVA 
analysis of covariance 
ATC 
Anatomical Therapeutic Chemical 
BBI 
Brickell Biotech, Inc. 
BMI 
body mass index 
CRF 
case report form 
CS (CSH) 
compound symmetry (heterogenous compound symmetry) 
CSR 
clinical study report 
DLQI 
Dermatology Life Quality Index 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ET 
Early Termination 
FOCBP 
female of childbearing potential 
GLIMMIX 
generalized linear mixed model 
GSP 
gravimetric sweat production 
HDSS 
Hyperhidrosis Disease Severity Scale 
HDSM-Ax 
Hyperhidrosis Disease Severity Measure-Axillary 
ICH 
International Conference on Harmonization 
mITT 
Modified Intent-to-Treat 
LOCF 
last observation carried forward 
LS 
least-square 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measures 
PP 
Per-Protocol 
PT 
preferred term 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SI 
Système International 
TEAE 
treatment-emergent adverse event 
TOEP (TOEPH) 
Toeplitz (heterogenous Toeplitz) 
 
 
 
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Abbreviation 
Definition  
UPT 
urine pregnancy test 
WHO 
World Health Organization 
 
 
 
 
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4 INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide comprehensive and detailed 
descriptions of the methods and presentation of data analyses proposed for Brickell Biotech, Inc.  
Protocol BBI-4000-CL-203 (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). Descriptions of planned 
analyses are provided in order to avoid post hoc decisions that may affect the interpretation of 
the statistical analysis. The statistical methods applied in the design and planned analyses of this 
study are consistent with the International Conference on Harmonisation (ICH) guideline 
Statistical Principals for Clinical Trials (1998).  
This SAP will be finalized prior to data analysis and before treatment unblinding and database 
lock to provide full details, including templates for tables, listings, and figures, to be presented in 
the clinical study report (CSR). Any changes between the statistical methods provided in the 
clinical study protocol and this SAP will be explained herein; any changes or deviations from 
this SAP relative to the final analysis will be fully documented in the CSR. Minor changes or 
deviations from the templates for tables, figures, and listings need not be documented in the 
CSR. 
5 STUDY OBJECTIVES 
5.1 
Primary Study Objectives 
The primary objectives of this study are to evaluate: 
1. 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 
2. The safety and local tolerability of BBI-4000 5%, 10% and 15% gel when applied 
topically in subjects with axillary hyperhidrosis. 
5.2 
Secondary Study Objective 
The secondary objective of this study is 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. 
 
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6 INVESTIGATIONAL PLAN 
6.1 
Overall Study Design 
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 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. Male or female subjects > 18 years of age in good general health and with a diagnosis 
of primary axillary hyperhidrosis in the opinion of the Investigator are eligible for study admission. 
Subjects will be randomized to receive BBI-4000 5%, or 10%, or 15% gel, or vehicle gel (vehicle) in 
a balanced ratio of 1:1:1:1. 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. BBI-
4000 vehicle (vehicle) gel will be identical in appearance and constituents to BBI-4000 
(sofpironium bromide) Gel but will not contain BBI-4000. The vehicle 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 vehicle 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 vehicle formulation. 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). 
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. See Table 2 for an overview of study events 
and timing. 
 
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6.2 
Schedule of Assessments 
Table 2 
Time and Events Table 
 
 
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.  
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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6.3 
Treatments 
6.3.1 
Treatments Administered 
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 (~ 0.56 g) of 
the gel formulation. BBI-4000 vehicle (vehicle) gel will be identical in appearance and 
constituents to BBI-4000 (sofpironium bromide) Gel, but will not contain the active ingredient, 
BBI-4000. Two vehicle pump containers are packaged in a carton with 4 applicators to match the 
active drug product kits. 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. One full 
pump actuation delivers enough gel to apply to one axillae.  
6.3.2 
Method of Assigning Subjects to Treatment Groups 
Subjects will be randomized to receive BBI-4000 5%, 10%, or 15% gel, or vehicle gel (vehicle) 
in a balanced ratio of 1:1:1:1. 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 case report 
form (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 due to newly discovered ineligibility, 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. 
6.4 
Efficacy and Safety Variables 
6.4.1 
Efficacy Variables 
The following assessment measures will be conducted to evaluate the efficacy of BBI-4000: 
• HDSM-Ax as measured by the subject 
 
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• GSP by the investigator 
• HDSS as measured by the subject 
• DLQI as measured by the subject 
6.4.1.1 
Primary Efficacy Variables 
The primary efficacy endpoint is improvement on the HDSM-Ax, 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 
6.4.1.2 
Secondary Efficacy Variables 
Secondary efficacy endpoints 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 ranked change from baseline in gravimetrically measured sweat production to end of 
therapy. 
6. 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. 
7. 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. 
8. The proportion of subjects achieving at least a 2-point improvement in HDSS from 
baseline to end of therapy. 
 
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9. The proportion of subjects achieving at least a 1-point improvement in HDSS from 
baseline to end of therapy. 
6.4.1.3 
Other Efficacy Variables 
Other efficacy endpoints are:  
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. Ranked change from baseline in gravimetrically measured sweat production at Days 8, 
15, 22, 29, 36, 41, 42, 43, and 57. 
8. 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. 
9. 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. 
10. 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. 
11. 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. 
12. Change in the modified DLQI from baseline to Day 43 (end of therapy). 
 
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6.4.2 
Description of Safety Variables 
The following safety assessment measures will be conducted: 
• Adverse events 
• Local tolerability assessments including burning, itching, dryness, scaling and erythema 
• Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) 
• Laboratory tests (hematology, chemistry, and urinalysis) and pregnancy testing in 
females of child bearing potential. 
6.4.2.1 
Adverse Events 
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.  
6.4.2.2 
Local Tolerability Assessments 
Local tolerability assessments 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. 
6.4.2.3 
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. 
 
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6.4.2.4 
Laboratory Parameters 
Hematology, clinical chemistry, urinalysis and additional parameters to be tested are listed in 
Table 3: 
Table 3 
Laboratory Tests 
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). 
6.5 
Data Quality Assurance 
Report summaries will be generated using validated Base SAS software, version 9.4 or higher, 
on a PC or server-based platform. Additional validated software may be used to generate 
analyses, as needed.  
All SAS programs that create outputs or supporting analysis datasets will be validated by a 
second statistical programmer or biostatistician. At a minimum, validation of programs will 
consist of a review of the program log, review of output or dataset format and structure, and 
independent confirmatory programming to verify output results or dataset content. Additionally, 
all outputs will undergo a review by a senior level team member before finalization. 
The content of the source data will be reviewed on an ongoing basis by project statistical 
programmers and statisticians. Data will be checked for missing values, invalid records, and 
extreme outliers through defensive programming applications, analysis-based edit checks, and 
 
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other programmatic testing procedures. All findings will be forwarded to the project data 
manager for appropriate action and resolution.  
7 STATISTICAL METHODS 
7.1 
General Methodology 
Data will be analyzed by Agility Clinical biostatistics personnel. Statistical analyses will be 
reported with tables, figures, and listings, presented in rich text format, and using recommended 
ICH numbering. Output specifications for all tables, figures, and listings will be in conformance 
with guidelines specified by the ICH in Appendix 7 of the Electronic Common Technical 
Document Specification (Apr 2003).  
7.1.1 
Reporting Conventions 
Tables and figures will be summarized by treatment group. Tables summarizing demographics 
and other baseline characteristics will also include a column for all subjects combined. In 
general, all data collected and any derived data will be presented in subject data listings, for all 
enrolled subjects. Listings will be ordered by site, subject number, treatment group, and 
assessment or event date. The treatment group presented in listings will be based on the planned 
assignment, unless otherwise noted. 
In general, continuous variables will be summarized to indicate the population sample size (N), 
number of subjects with available data (n), mean, SD, median, minimum, and maximum values. 
Categorical variables will be summarized by the population size (N), number of subjects with 
available data (n), number of subjects in each category, and the percentage of subjects in each 
category. Unless otherwise noted, the denominator to determine the percentage of subjects in 
each category will be based on the number of subjects with available data. Select ordinal data 
may be summarized using both descriptive statistics and counts and percentages of subjects in 
each category, as appropriate. 
Non-zero percentages will be rounded to one decimal place. Rounding conventions for 
presentation of summary statistics will be based on the precision of the variable of 
summarization, as it is collected in its rawest form (i.e., on the electronic case report form 
[eCRF] or as provided within an external file) and are outlined as follows: 
• The mean and median will be rounded to one more decimal place than the precision of 
the variable of summarization; 
• Measures of variability (e.g., SD, SE) will be rounded to two more decimal places than 
the precision of the variable of summarization; and 
• Minimum and maximum values will be presented using the same precision as the 
variable of summarization. 
 
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Other statistics (e.g., CIs) will be presented using the same general rules outlined above, or 
assessed for the most appropriate presentation based on the underlying data. 
Statistical significance testing will be one-sided as described in Section 7.4.4.1, and performed 
using α=0.10. P-values will be reported for all statistical tests, rounded to four decimal places. P-
values less than 0.0001 will be displayed as “<0.0001”; p-values greater than 0.9999 will be 
displayed as “>0.9999”. Tests of interaction terms, if applicable, will be two-sided and 
performed using α=0.10. 
7.1.2 
Standard Calculations 
Where appropriate, the calculated study day of each assessment or event will be presented with 
the assessment or event date on subject data listings, where study day will be determined as: 
• The assessment/event date minus the date of first dose, if the assessment/event date is 
prior to the date of first dose; and 
• The assessment/event date minus the date of first dose, plus one, if the assessment/event 
date is on or after the date of first dose. 
Other variables requiring calculations will be derived using the following formulas: 
• Days: A duration between two dates expressed in days will be calculated using the 
following conventions: 
o Later date – earlier date + 1, if the earlier date is on or after the date of first dose 
of study drug; or 
o Later date – earlier date, if the earlier date is prior to the date of first dose of study 
drug. 
• Change from Baseline: Change from baseline will be calculated as the post-baseline 
value minus the baseline value; 
• Percentage Change from Baseline: Percentage change from baseline will be calculated 
as the change from baseline divided by the baseline value, multiplied by 100. 
• Rank Transformation: All raw data will be ranked together within time point without 
regard to treatment group, from smallest value to highest value. The smallest observation 
will be assigned the rank of 1, the second smallest the rank of 2, and so on. Average 
ranks will be used for tied observations. 
Unless otherwise noted, values reported as greater than or less than some quantifiable limit (e.g., 
“< 1.0”) will be summarized with the sign suppressed in summary tables and figures, using the 
numeric value reported. Data will display on subject listings to include the sign. 
 
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7.2 
Analysis Populations 
The analysis populations are defined as follows:  
• Safety Population: Includes all subjects randomized in the study who received study drug 
at least once. Subjects will be included in the treatment group based on the lowest dose of 
active treatment they actually received (even if not the treatment group to which they 
were randomized). Thus, a subject randomized to 15% BBI-4000 but who actually 
received 10% and 5% would be included in the 5% BBI-4000 group. A subject 
randomized to vehicle but who actually received 5% and 10% would be included in the 
5% BBI-4000 group. 
• Modified Intent-to-Treat (mITT) Population: Includes 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. 
• Per-Protocol (PP) Population: Includes all Safety Population subjects who meet the 
following criteria: 
1. Meets the inclusion/exclusion criteria 
2. Has not taken or applied any interfering concomitant medications. 
3. Completed the following visits: 
• Visit 2 GSP 1, and the required GSP data collection 
• Visit 3 GSP 2, and the required GSP data collection 
• Visit 4 GSP 3, and the required GSP data collection 
• Visit 11 GSP 4, and the required GSP data collection 
• Visit 12 GSP 5, and the required GSP data collection 
• Visit 13 GSP 6, and the required GSP data collection 
Subjects will be included in the treatment group based on the treatment actually received, 
as described above. 
Data summaries to be presented on both the Safety Population and the mITT Population will 
only be produced on both analysis sets if there is a difference in the population groups (e.g., at 
least one subject receives a different treatment than they were originally assigned or some 
subjects never received any protocol treatment).   
 
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7.3 
Study Subjects 
7.3.1 
Disposition of Subjects 
Subject disposition will be summarized for all randomized subjects by treatment group and over 
all subjects combined. Summaries will include the number and percentage of subjects in each 
analysis population, completing the study, and discontinuing the study early by the primary 
reason for discontinuation. Subject disposition will also be summarized separately for each study 
center. 
7.3.2 
Protocol Deviations 
Major protocol violations will be summarized by treatment group and over all subjects combined 
for the Safety Population. Major protocol violations may include, but will not be limited to the 
following: 
• 
Violation of eligibility criteria; 
• 
Randomization error;  
• 
Non-compliance with study drug dosing; 
• 
On-study administration of a prohibited medication;  
• 
Unauthorized changes to protocol procedure that could potentially affect subject safety or 
are a flagrant deviation of protocol defined procedures  
All major protocol violations will be determined and appropriately categorized prior to database 
lock and prior to breaking the blind of the treatment group assignments. The number and 
percentage of subjects with any major protocol violations as well as the number and percentage 
of subjects with violations within each category will presented. A per subject listing will be 
provided for all protocol violations. All protocol violations will be determined and appropriately 
categorized prior to database lock.  
7.4 
Efficacy 
7.4.1 
Datasets Analyzed 
All efficacy summaries will be based on the mITT Population; select efficacy summaries will 
also be produced on the PP Population. A data listing of subjects excluded from the mITT or PP 
Population, to include the reason for exclusion, will be presented. 
7.4.2 
Demographic and Other Baseline Characteristics 
Demographic variables including age, sex, ethnicity and race, will be summarized by treatment 
group and over all subjects combined for the Safety, mITT, and PP Populations.  
 
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Age will be summarized using descriptive statistics. Sex, ethnicity, and race will be summarized 
with the number and percentage of subjects in each parameter category. 
Baseline characteristics include medical history, height, weight, time since onset of axillary 
hyperhidrosis symptoms and body mass index (BMI). BMI will be calculated as: weight (kg) / 
(height (cm) / 100)2. Time since onset of axillary hyperhidrosis symptoms will be reported in 
months and calculated by dividing the duration in days by (365.25 / 12). Baseline characteristics 
will be summarized for the Safety Population by treatment group and for all subjects combined. 
Height, weight, and BMI at baseline will be summarized using descriptive statistics. Medical 
history events will be coded to system organ class using the Medical Dictionary for Regulatory 
Activities (MedDRA, version 19.1). Frequency counts and percentages to summarize subjects 
reporting abnormal medical history by system organ class as will be presented. 
7.4.3 
Measurements of Treatment Compliance 
Study drug compliance will be calculated for each subject by taking into account whether a 
subject took all doses of study drug as instructed through dosing deviations collected on the 
CRF. Compliance to the study treatment regimen will be determined as the total number of doses 
received divided by the number of expected doses, multiplied by 100. As study drug is applied 1 
time daily per axilla for 42 days, the expected number of doses will be the number of days 
between the date of last dose of study drug minus the date of first dose of study drug, plus one, 
times two. The number of doses received will be the number of days between the date of last 
dose of study drug minus the date of first dose of study drug, plus one, times 2 minus the number 
of missed doses recorded on the Dosing page of the CRF. Dosing compliance will be 
summarized using descriptive statistics based on the Safety Population, and separately based on 
the PP Population. 
7.4.4 
Primary Efficacy Endpoint Analysis Methods 
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. Baseline and End of therapy values are defined as follows. 
• 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. 
• End of Therapy Imputed value = includes subjects missing all end of therapy values, 
where data is imputed by the last three available post-baseline visits. 
   
 
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7.4.4.1 
Primary Efficacy ANCOVA 
The primary efficacy endpoint is the change from baseline to the end of therapy in the mean 
HDSM-Ax score. The primary efficacy endpoint will be analyzed both as a continuous measure 
and as a binary outcome. As a continuous measure, the HDSM-Ax change scores will be 
compared between treatment groups in pairwise fashion by an ANCOVA model adjusting for the 
baseline HDSM-Ax score. The analysis will be performed with no imputation of missing data.  
As a binary measure, i.e. achieving a ≥ 1-point improvement or not from baseline to end of 
therapy, a binary logistic regression will be performed with treatment assignment and baseline 
HDSM-Ax score as independent variables in the model. Any subject without a definable 1-point 
improvement (e.g., missing data) between Baseline and End of Treatment will be considered a 
non-responder. P values will generally be regarded as descriptive and statistical significance will 
be assessed using a gate-keeping hierarchy as described in Section 7.4.6.5 for both the 
continuous measure and binary data analyses.   
The null hypothesis to be tested for the continuous measure is as below: 
 
H0:  µA ≥ µP;  
where µA and µP represent the true underlying mean change scores for Treatment A (active drug) 
and Treatment P (vehicle), respectively. The alternate hypothesis to be tested is that the true 
active treatment group mean change score is smaller than the true vehicle group mean change 
score: 
 
H1:  µA < µP;  
Tested in the logit scale, the null hypothesis for the dichotomous outcome is that the true 
proportion of subjects with a 1 point or more improvement is lower in the active treatment group: 
H0:  PA ≤ PP; 
The alternate hypothesis to be tested is that the true proportion of subjects with a 1 point or more 
improvement is higher in the active treatment group: 
H1:  PA > PP; 
 
 
7.4.4.2 
Sensitivity Analysis by Mixed Effects Models 
As a method that is known to be robust to missing data, mixed model repeated measures 
(MMRM) analyses will also be performed for the primary efficacy endpoint using all available 
HDSM-Ax change from baseline data on study days 8, 15, 22, 29, 36, and end of therapy. As 
fixed effects, treatment (active treatment group or vehicle gel), baseline HDSM-Ax score and 
visit (included in the class statement as a class variable) and baseline*visit interactions will be 
 
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included in the model both without and with treatment*visit interaction terms. Subject will be 
analyzed as a random effect. Similarly, MMRMs will also be performed for the primary efficacy 
endpoint using HDSM-Ax dichotomized response data, and HDSM-Ax + GSP dichotomized 
response data. The models will be the same as the model for continuous data but the dependent 
variable of interest will be the response status with a logit link, using the SAS Proc GLIMMIX 
module.  Both the heterogeneous CS (CSH) and TOEP (TOEPH) covariance structures will be 
considered and the structure with lower AIC will be used. The percentage of responders will also 
be summarized at each visit in the result table.  
MMRM analysis as described above will also be performed for continuous GSP data (both 
Normal model and using rank transformed data) and binary GSP response (i.e. 50% reduction 
from baseline) data. 
7.4.4.3 
Additional Sensitivity Analysis 
An additional sensitivity analysis will be performed as follows. For subjects missing all 3 end of 
therapy values, the data will be imputed by the last three available post-baseline (i.e., from Day 8 
onward) assessment values. This analysis will be performed for both the continuous data analysis 
and the binary data analysis using the same ANCOVA models as described above. 
7.4.5 
Secondary and Other Efficacy Endpoint Analysis Methods 
Baseline and End of Therapy values for HDSS and GSP are defined as follows. 
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. 
• End of Therapy Imputed value = includes subjects missing all end of therapy values, 
where data is imputed by the last three available post-baseline visits. 
Gravimetric Sweat Production (both axilla combined total): 
• Baseline value = the median of GSP1, GSP2, and GSP3 measurements obtained on Visit 
2, Visit 3, and Visit 4, respectively. The mean value of the same visits will also be used 
for analysis. 
• End of Therapy value = the median of GSP4, GSP5, and GSP6 measurements obtained 
on Visit 11, Visit 12, and Visit 13, respectively. The mean value of the same visits will 
also be used for analysis. 
 
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• End of Therapy Imputed value = includes subjects missing all end of therapy values, 
where data is imputed by the last three available post-baseline visits. 
• Where data from a single axilla is missing, data will be imputed by using the median of 
the last 3 available values for that axilla. 
• Analyses of continuous data will be performed using both Normal model and rank-
transformed data. 
DLQI: 
The DLQI total score is calculated by summing answers to questions 1 through 10, including 
both parts of Question 7. All questions must be answered at the first DLQI assessment. 
Subsequent DLQI assessments with a single missing answer will be scored 0 for that question 
and totaled. Subjects with more than one missing question will have the instrument dropped for 
that visit. 
The DLQI’s change from baseline at 43 days (Visit 13) will be compared between each BBI-
4000 active arm and the vehicle arm using an ANCOVA model adjusting for the baseline DLQI 
score. 
With the exception of DLQI, analysis for secondary and other efficacy endpoints will generally 
be similar to the HDSM-Ax analysis described in Section 7.4.4.1 and Section 7.4.4.3. For GSP 
results analyzed as continuous measures, analyses assuming Normality for the data distribution 
(i.e., comparing means) will be performed using ANCOVA as described in Section 7.4.4. In 
addition, continuous gravimetric change scores will also be analyzed with rank transformed data 
using the t test for ANCOVA models. For both Normal model and non-parametric ANCOVA, 
treatment and baseline value will be the independent variables and continuous gravimetric 
change scores or rank scores (of change values) will be the dependent variable as appropriate.  
All non-primary analyses will be based on available data without missing data imputation unless 
otherwise specified.  
A table by treatment arm and visit summarizing the number of subjects with non-missing data 
will be also provided for HDSM-Ax, HDSS, and GSP. Subjects with non-missing data will be 
summarized for Visits 1 and 4, combined, Visit 1, Visit 4, and missing data at both Visit 1 and 
Visit 4. The number of subjects with non-missing data at each of Visits 6 through Visit 14 will 
be summarized, and subjects with complete data at Visits 11, 12, and 13, combined, any 2 of the 
three (Visit 11, 12, or 13), any one of the three, and subjects missing data at all of Visits 11 
through 13 will be summarized. 
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-
 
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Ax, HDSS and gravimetrically measured sweat production), stability, reliability, ability to detect 
change, and interpretability of clinical trial results. The psychometric evaluation is outside the 
scope of this SAP and will be described in a separate analysis plan. 
7.4.6 
Statistical/Analytical Issues 
7.4.6.1 
Adjustments for Covariates 
The ANCOVA model and binary logistic regression model to compare treatment groups for the 
primary endpoint will include a covariate adjustment for the baseline value. Select secondary 
endpoints will be analyzed similarly.  
7.4.6.2 
Handling of Dropouts or Missing Data 
Generally, no imputations will be performed on missing data; all analyses will be based on 
observed data unless otherwise specified. 
7.4.6.3 
Interim Analyses and Data Monitoring 
There are no interim analyses planned, nor is there a plan to establish a data monitoring 
committee for this study. 
7.4.6.4 
Multicenter Studies 
This is a multicenter study, with approximately 25 sites expected to participate. Data collected 
from all study centers will be pooled for data analysis. The effect of study center on the efficacy 
analysis results may be explored post-hoc, as needed. 
7.4.6.5 
Multiple Comparisons/Multiplicity 
To limit the study-wide false positive rate to 0.10, a gate-keeping hierarchical testing algorithm 
will be employed to assess statistical significance regarding the primary analyses for the primary 
efficacy endpoint, i.e. ANCOVA analyses on change from baseline in HDSM-Ax score. The 
hierarchy is, the comparison between BBI-4000 15% group and vehicle group will be considered 
first, if the result is favorable with a 1-sided p<0.10, then the comparison between BBI-4000 
10% group and vehicle will be considered. Similarly, if the BBI-4000 10% group is favorable 
with a 1-sided p<0.10, then comparison between BBI-4000 5% group and vehicle will be 
considered.  The same gate keeping hierarchical testing algorithm will be employed for both the 
binary data analysis and the continuous measurement analysis.  
The primary efficacy analysis will be performed on the mITT population; the PP population will 
be utilized for selected efficacy analyses. The PP population is described in Section 7.2. 
 
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7.4.6.6 
Active-Control Studies Intended to Show Equivalence 
This study does not include an active-control product and is not intended to demonstrate 
equivalence between any two drug products. 
7.4.6.7 
Examination of Subgroups 
There are no planned analyses to assess efficacy results by subgroups. 
7.5 
Safety Analysis 
Safety analysis will be carried out for the Safety Population, to include all subjects who receive 
at least one dose of study drug. Subjects who do not complete the study, for whatever reason, 
will have all available data up until the time of termination included in the analysis. For safety 
analysis presented by study visit, the baseline value will be defined as the last value reported 
prior to first study drug administration. 
7.5.1 
Extent of Exposure 
Extent of exposure to study treatment will be summarized for the Safety Population by treatment 
group. The duration of exposure will be presented in days and calculated as the date of last dose 
of study drug minus the date of first dose of study drug, plus one. Duration of exposure will be 
summarized using descriptive statistics. Drug (pump) dispensation will be provided in a listing, 
to include total drug delivered per subject.  Each pump will be primed, then weighed, prior to 
dispensing pumps to subjects. Each pump will be weighed upon return. Total drug delivered will 
be calculated as the total weight of all pumps dispensed minus the total weight of all returned 
pumps. 
7.5.2 
Adverse Events 
Treatment-emergent adverse events (TEAEs) are defined as those adverse events (AEs) with 
onset after the first dose of study drug or existing events that worsened after the first dose during 
the study. Treatment-emergent AEs will be summarized by treatment group. Events reported 
with a partial onset date (e.g., month and year are reported but the day is missing) will be 
considered to be treatment-emergent if it cannot be confirmed that the event onset was prior to 
the first dose of study drug based on the available date entries. 
Verbatim terms on case report forms will be mapped to preferred terms and system organ classes 
using MedDRA version 19.1.   
Summaries that are displayed by system organ class and preferred terms will be ordered by 
descending incidence of system organ class in the combined BBI-4000 group and preferred term 
within each system organ class. Summaries displayed by preferred term only will be ordered by 
descending incidence of preferred term in the combined BBI-4000 group. Summaries of the 
following types will be presented: 
 
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• Overall summary of number of unique TEAEs and treatment-emergent serious adverse 
events (SAEs) and subject incidence of TEAEs meeting various criteria; 
• Subject incidence of TEAEs by MedDRA system organ class and preferred term; 
• Subject incidence of the most frequently-occurring TEAEs (i.e., TEAEs occurring in ≥ 
10% of the Safety Population) by MedDRA system organ class and preferred term; 
• Subject incidence of TEAEs related to study drug by MedDRA system organ class and 
preferred term; 
• Subject incidence of TEAEs by severity grade, MedDRA system organ class, and 
preferred term; 
• Subject incidence of TEAEs related to Study Drug by severity, MedDRA system organ 
class and preferred term; and, 
• Subject incidence of SAEs by MedDRA system organ class and preferred term 
• Subject incidence of SAEs related to study drug by MedDRA preferred term. 
At each level of summarization (e.g., any AE, system organ class, and preferred term), subjects 
experiencing more than one TEAE will be counted only once. In the summaries of TEAEs by 
severity grade, subjects will be counted once at the highest severity reported at each level of 
summarization, and by each level of severity; in the summary of TEAEs by relationship, subjects 
will be counted once at the closest relationship to study drug.  
Adverse event data will be presented in data listings by subject, treatment group, and event. 
Serious AEs and AEs leading to discontinuation of the study drug will be presented in separate 
data listings. 
7.5.3 
Local Tolerability Assessments 
Subject and Investigator assessments will be included in separate tables and listings, with the 
count and percentage of subjects within each severity (maximum severity assessed at either 
axilla) and treatment group presented by parameter and visit.  
7.5.4 
Deaths, Other Serious Adverse Events, and Other Significant Adverse Events 
All deaths during the study, including the post-treatment follow-up period, will be listed by 
subject, to include the primary cause of death and investigator narratives. Serious AEs and other 
significant AEs, including those that led to withdrawal, interruption, or dose reduction of the 
study drug, will be provided in separate subject data listings. 
 
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7.5.5 
Clinical Laboratory Evaluation 
All descriptive summaries of laboratory results will be based on data analyzed by the central 
laboratory and presented in Système International (SI) units, as suggested by the Center for 
Biologics Evaluation and Research and the Center for Drug Evaluation and Research Position on 
Use of SI Units for Lab Tests (Oct 2013). All data will be included in by-subject data listings. 
Laboratory measurements identified as abnormal (i.e., outside the normal range) will also be 
listed separately by subject, laboratory test, and unit. 
Clinical laboratory measurements, including serum chemistry and hematology, will be 
summarized by treatment group. Descriptive statistics will be presented for observed values and 
changes from baseline at each visit where parameters were scheduled to be collected per the 
clinical study protocol.  
Where applicable, laboratory results will be classified as “low,” “normal,” or “high” with respect 
to the parameter-specific reference ranges (i.e., below the lower limit of the normal range, within 
the normal range, or above the upper limit of the normal range). Three-by-three contingency 
tables will be presented for each laboratory parameter to summarize the shift from the baseline 
category to the worst post-baseline measurement, defined as the value numerically farthest 
outside of the normal range across all post-baseline visits through the end of the study. 
Summary results will include the count and percentage of subjects within each shift category and 
treatment group. 
7.5.6 
Vital Signs, Physical Findings, and Other Observations Related to Safety 
7.5.6.1 
Vital Signs 
Vital sign parameter measurements will be summarized by treatment group. Descriptive statistics 
will be presented for results and change from baseline at each visit where parameters were 
scheduled to be collected.  
7.5.6.2 
Physical Examination 
Results of the physical examination will be presented in subject data listings by subject, study 
visit, and body system. 
7.5.6.3 
Prior and Concomitant Medications 
Medications will be coded using the World Health Organization (WHO) drug dictionary, 
enhanced (version B2 March 1, 2016). Medications entered on the eCRF will be mapped to 
Anatomic Therapeutic Chemical (ATC) drug class (level 4) and drug name.  
Prior and concomitant medications will be summarized separately and the study phase of each 
medication will be determined programmatically based on medication start and end dates. A 
 
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prior medication is defined as any medication administered prior to the date of the first dose of 
study drug. A concomitant medication is defined as any medication administered on or after the 
date of the first dose of study drug. A medication may be defined as both prior and concomitant. 
If it cannot be determined whether a medication was received prior to the start of study drug 
dosing due to partial or missing medication start and/or end dates, it will be considered a prior 
medication. Likewise, if it cannot be determined whether a medication was received after the 
start of study drug dosing, it will be considered concomitant. 
For the summary of both prior medications and concomitant medications, the number and 
percentage of subjects receiving any medication will be summarized by treatment group, as will 
the number and percentage receiving any medication by ATC drug class and generic drug name. 
Subjects reporting use of more than one medication at each level of summarization (any 
medication received, ATC class, and generic drug name) will be counted only once. ATC class 
terms will be displayed by descending order of incidence, as will generic drug names within each 
ATC class. The study phase during which each medication was received (e.g., prior, 
concomitant, or both) will be presented on the listing of prior and concomitant medications. 
7.5.6.4 
Prior and Concomitant Therapies/Procedures 
Therapies/Procedures will be coded using MedDRA version 19.1. Therapies entered on the 
eCRF will be mapped to SOC. 
The study phase of each therapy/procedure will be determined programmatically based on start 
and end dates. A prior therapy/procedure is defined as any therapy/procedure occurring prior to 
the date of the first dose of study drug. A concomitant therapy/procedure is defined as any 
therapy/procedure occurring on or after the date of the first dose of study drug. A 
therapy/procedure may be defined as both prior and concomitant. If it cannot be determined 
whether a therapy/procedure occurred prior to the start of study drug dosing due to partial or 
missing, it will be considered a prior therapy/procedure. Likewise, if it cannot be determined 
whether a therapy/procedure occurred after the start of study drug dosing, it will be considered 
concomitant. Therapies and procedures will be reported in a subject listing, and identified as 
prior or concomitant, and as a therapy or a procedure. 
7.6 
Determination of Sample Size 
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, the true response rates will be 
assumed 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.  
For the continuous version of HDSM-Ax change from baseline to end of therapy, the true mean 
difference between each BBI-4000 arm and the vehicle arm will be assumed to be 0.18, with a 
common standard deviation of 0.36, i.e., an effect size (mean difference/standard deviation) of 
 
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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.  
Assuming an approximate 10% non-evaluable rate for the mITT primary efficacy analyses, 220 
randomized subjects are targeted for enrollment. 
7.7 
Changes in the Conduct of the Study or Planned Analyses  
Analysis of change in DLQI score between baseline and Day 57 removed as this data is not 
collected. 
An explanation of how subjects receiving multiple doses will be assigned to dosage groups in the 
Safety Population was added. 
ITT population was changed to mITT population. 
The Per Protocol population definition was changed to a subset of the Safety population, as 
subjects must receive one dose of study drug. 
An Imputed End of Therapy time point added to primary and secondary outcomes as a sensitivity 
analysis. 
GSP data to be analyzed separately with baseline/EOT mean value and baseline/EOT median 
value.  
MMRM sensitivity analysis expanded to include GSP continuous (raw and ranked) data, and a 
logit-linked, generalized MMRM analysis of HDSM-Ax, GSP, and HDSM-Ax+GSP binary 
outcomes. 
7.8 
Changes in SAP from Version 1.0 to Version 2.0 
Table summaries of the MMRM sensitivity analysis expanded to include GSP continuous 
(Normal model and ranked) data, and a logit-linked, generalized MMRM analysis of GSP 
change from baseline binary outcomes. 
8 REFERENCE LIST 
International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use. Statistical principles for clinical trials (E9). International 
Conference on Harmonization; 1998. 
M2 eCTD: Electronic Common Technical Document Specification Appendix 7, provided by the 
International Conference on Harmonization. Available from: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/u
cm073240.pdf 
 
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Data Standards: Position on Use of SI Units for Lab Tests. U.S Food and Drug Administration; 
25 October 2013. Available from: 
http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/ucm372553.htm  
 
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APPENDIX A: LIST OF TABLES, FIGURES AND DATA LISTINGS 
List of Tables 
Number 
Description 
Analysis Set 
Source Listing(s) 
14.1 
Demographic Data 
Summaries 
 
 
14.1.1.1 
Subject Disposition  
All Randomized 
Subjects 
16.2.1 
14.1.1.2 
Subject Disposition by 
Study Center  
All Randomized 
Subjects 
16.2.1 
14.1.2 
Major Protocol Deviations  
Safety 
Population 
16.2.2.1 
14.1.3.1 
Demographics 
Safety 
Population 
16.2.4.1 
14.1.3.2 
Demographics 
mITT 
Population 
16.2.4.1 
14.1.3.3 
Demographics 
PP Population 
16.2.4.1 
14.1.4.1 
Baseline Characteristics  
Safety 
Population 
16.2.9.1; 16.2.4.2 
14.1.4.2 
Baseline Characteristics  
mITT 
Population 
16.2.9.1; 16.2.4.2 
14.1.5 
Medical History  
Safety 
Population 
16.2.4.2 
14.1.6 
Prior Medications 
Safety 
Population 
16.2.9.3 
14.1.7 
Prior Therapy and 
Procedures 
Safety 
Population 
16.2.9.4 
14.2 
Efficacy Data Summary 
Tables 
 
 
14.2.1.1 
HDSM-Ax Summary of 
First and Last Visits 
mITT 
Population 
16.2.6.1 
14.2.1.2 
HDSM-Ax Summary of 
First and Last Visits 
PP Population 
16.2.6.1 
14.2.1.3 
HDSM-Ax End of Therapy 
Change from Baseline 
ANCOVA  
mITT 
Population 
16.2.6.1 
14.2.1.4 
HDSM-Ax End of Therapy 
Change from Baseline 
ANCOVA  
PP Population 
16.2.6.1 
 
Confidential 
 
Page 31 of 122 
 


Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
Number 
Description 
Analysis Set 
Source Listing(s) 
14.2.1.5 
HDSM-Ax Change from 
Baseline MMRM and 
Change from Baseline by 
Visit ANCOVA 
mITT 
Population 
16.2.6.1 
14.2.1.6 
HDSM-Ax Change from 
Baseline MMRM and 
Change from Baseline by 
Visit ANCOVA 
PP Population 
16.2.6.1 
14.2.1.7 
HDSM-Ax Responder 
MMRM 
mITT 
Population 
16.2.6.1 
14.2.1.8 
HDSM-Ax Responder 
MMRM 
PP Population 
16.2.6.1 
14.2.2.1 
HDSM-Ax and GSP 
Responder MMRM 
mITT 
Population 
16.2.6.1; 16.2.6.2 
14.2.2.2 
HDSM-Ax and GSP 
Responder MMRM 
PP Population 
16.2.6.1; 16.2.6.2 
14.2.3.1 
GSP Summary of First and 
Last Visits 
mITT 
Population 
16.2.6.2 
14.2.3.2 
GSP Summary of First and 
Last Visits 
PP Population 
16.2.6.2 
14.2.3.3 
Summary of Missing 
Singular Axilla GSP 
Measurements 
mITT 
Population 
16.2.6.2 
14.2.3.4 
Summary of Missing 
Singular Axilla GSP 
Measurements 
PP Population 
16.2.6.2 
14.2.3.5 
GSP End of Therapy 
Change from Baseline 
ANCOVA 
mITT 
Population 
16.2.6.2 
14.2.3.6 
GSP End of Therapy 
Change from Baseline 
ANCOVA 
PP Population 
16.2.6.2 
14.2.3.7 
GSP End of Therapy 
Change from Baseline 
ANCOVA for Ranked 
Values 
mITT 
Population 
16.2.6.2 
14.2.3.8 
GSP End of Therapy 
Change from Baseline 
ANCOVA for Ranked 
Values 
 
PP Population 
16.2.6.2 
 
Confidential 
 
Page 32 of 122 
 


Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
Number 
Description 
Analysis Set 
Source Listing(s) 
14.2.3.9 
GSP Change from Baseline 
MMRM and Change from 
Baseline by Visit ANCOVA 
mITT 
Population 
16.2.6.2 
14.2.3.10 
GSP Change from Baseline 
MMRM and Change from 
Baseline by Visit ANCOVA 
PP Population 
16.2.6.2 
14.2.3.11 
GSP Change from Baseline 
MMRM and Change from 
Baseline by Visit ANCOVA 
for Ranked Values 
mITT 
Population 
16.2.6.2 
14.2.3.12 
GSP Change from Baseline 
MMRM and Change from 
Baseline by Visit ANCOVA 
for Ranked Values 
PP Population 
16.2.6.2 
14.2.3.13 
GSP Responder MMRM 
mITT 
Population 
16.2.6.2 
14.2.3.14 
GSP Responder MMRM 
PP Population 
16.2.6.2 
14.2.4.1 
HDSS Summary of First 
and Last Visits  
mITT 
Population 
16.2.6.3 
14.2.4.2 
HDSS Summary of First 
and Last Visits  
PP Population 
16.2.6.3 
14.2.4.3 
HDSS Responder 
Regression  
mITT 
Population 
16.2.6.3 
14.2.4.4 
HDSS Responder 
Regression  
PP Population 
16.2.6.3 
14.2.5.1 
DLQI Change Score 
ANCOVA  
mITT 
Population 
16.2.6.4 
14.2.5.2 
DLQI Change Score 
ANCOVA  
PP Population 
16.2.6.4 
14.3 
Safety Data Summaries 
 
 
14.3.1  
Displays of Adverse 
Events 
 
 
14.3.1.1 
Overall Summary of 
Treatment-Emergent 
Adverse Events  
Safety 
Population 
16.2.7.1 
14.3.1.2 
Treatment-Emergent 
Adverse Events by System 
Organ Class and Preferred 
Term 
Safety 
Population 
16.2.7.1 
 
Confidential 
 
Page 33 of 122 
 


Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
Number 
Description 
Analysis Set 
Source Listing(s) 
14.3.1.3 
Most Frequently-Occurring 
(≥ 10% Overall) Treatment-
Emergent Adverse Events 
by System Organ Class, and 
Preferred Term  
Safety 
Population 
16.2.7.1 
14.3.1.4 
Treatment-Emergent 
Adverse Events Related to 
Study Drug by Preferred 
Term 
Safety 
Population 
16.2.7.1 
14.3.1.5 
Treatment-Emergent 
Adverse Events by Severity, 
System Organ Class, and 
Preferred Term 
Safety 
Population 
16.2.7.1 
14.3.1.6 
Treatment-Emergent 
Adverse Events Related to 
Study Drug by Severity, 
System Organ Class and 
Preferred Term 
Safety 
Population 
16.2.7.1 
14.3.1.7 
Treatment-Emergent 
Serious Adverse Events by 
System Organ Class and 
Preferred Term 
Safety 
Population 
14.3.2.2 
14.3.1.8 
Treatment-Emergent 
Serious Adverse Events 
Related to Study Drug by 
Preferred Term 
Safety 
Population 
14.3.2.2 
14.3.1.9 
Local Tolerability 
Assessments-Subject 
Assessments 
Safety 
Population 
16.2.7.2 
14.3.1.10 
Local Tolerability 
Assessments-Investigator 
Assessments 
Safety 
Population 
16.2.7.3 
14.3.2 
Listing of Deaths, Other 
Serious and Significant 
Adverse Events 
 
 
14.3.2.1 
Listing of Deaths  
Safety 
Population 
N/A 
14.3.2.2 
Listing of Serious Adverse 
Events  
Safety 
Population 
N/A 
 
Confidential 
 
Page 34 of 122 
 


Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
Number 
Description 
Analysis Set 
Source Listing(s) 
14.3.2.3 
Listing of Adverse Events 
Leading to Study Drug 
Discontinuation, Reduction 
or Interruption 
Safety 
Population 
N/A 
14.3.3 
Narratives of Deaths, Other 
Serious Adverse Events, 
and Certain Other 
Significant Adverse Events* 
 
 
14.3.4 
Abnormal Laboratory 
Values Listing 
 
 
14.3.4.1 
Listing of Abnormal 
Hematology Values  
Safety 
Population 
16.2.8.1 
14.3.4.2 
Listing of Abnormal 
Chemistry Values  
Safety 
Population 
16.2.8.2 
14.3.4.3 
Listing of Abnormal 
Urinalysis Values  
Safety 
Population 
16.2.8.3 
14.3.5 
Extent of Exposure 
 
 
14.3.5.1 
Extent of Exposure  
Safety 
Population 
16.2.5.1 
14.3.5.2 
Study Drug Compliance  
Safety 
Population 
16.2.5.2 
14.3.6 
Laboratory Summaries 
 
 
14.3.6.1 
Hematology – Univariate 
Summary by Parameter and 
Visit 
Safety 
Population 
14.3.4.1, 16.2.8.1 
14.3.6.2 
Hematology – Shift from 
Baseline to Worst Post-
Baseline Value by 
Parameter 
Safety 
Population 
14.3.4.1, 16.2.8.1 
14.3.6.3 
Chemistry – Univariate 
Summary by Parameter and 
Visit 
Safety 
Population 
14.3.4.2, 16.2.8.2 
14.3.6.4 
Chemistry – Shift from 
Baseline to Worst Post-
Baseline Value by 
Parameter 
Safety 
Population 
14.3.4.2, 16.2.8.2 
14.3.7 
Vital Signs, Physical 
Findings and Other 
Observations 
 
 
 
Confidential 
 
Page 35 of 122 
 


Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
Number 
Description 
Analysis Set 
Source Listing(s) 
14.3.7.1 
Vital Signs – Univariate 
Summary by Parameter and 
Visit 
Safety 
Population 
16.2.9.1 
14.3.7.2 
Concomitant Medications  
Safety 
Population 
16.2.9.3 
14.3.7.3 
Concomitant Therapy and 
Procedures 
Safety 
Population 
16.2.9.4 
*Narratives of deaths, other serious adverse events, and certain other significant adverse events 
will not be generated by analysis programming and are outside the scope of this analysis plan.  
 
 
 
Confidential 
 
Page 36 of 122 
 


Brickell Biotech, Inc. 
Statistical Analysis Plan
BBI-4000-CL-203 
 
Version 2.0; 27 July 2017
 
Subject Data Listings 
Number 
Description 
16.1.7 
Randomization 
16.1.7 
Randomization Scheme and Codes 
16.2.1 
Discontinued Subjects 
16.2.1 
Subject Disposition 
16.2.2 
Protocol Deviations 
16.2.2.1 
Protocol Violations/Deviations 
16.2.2.2 
Informed Consent and Eligibility Criteria 
16.2.3 
Subjects Excluded from the Efficacy Analysis 
16.2.3 
Subjects Excluded from the Efficacy Analysis 
16.2.4 
Demographic Data 
16.2.4.1 
Demographics 
16.2.4.2 
Medical History 
16.2.5 
Compliance and/or Drug Concentration Data 
16.2.5.1 
Study Drug Dosing 
16.2.5.2 
Study Drug Administration and Accountability  
16.2.5.3 
Study Drug Exposure and Compliance 
16.2.6 
Individual Efficacy Response Data 
16.2.6.1 
Hyperhidrosis Disease Severity Measure - Axillary 
16.2.6.2 
Gravimetric Sweat Production Measurements 
16.2.6.3 
Hyperhidrosis Disease Severity Scale 
16.2.6.4 
Dermatology Life Quality Index 
16.2.7 
Adverse Events 
16.2.7.1 
Adverse Events 
16.2.7.2 
Local Tolerability Assessments – Subject Assessments 
16.2.7.3 
Local Tolerability Assessments – Investigator Assessments 
16.2.8 
Listing of Individual Laboratory Measurements 
16.2.8.1 
Hematology 
16.2.8.2 
Chemistry 
16.2.8.3 
Urinalysis 
16.2.8.4 
Urine Pregnancy Test 
16.2.9 
Additional Safety Listings 
16.2.9.1 
Vital Signs 
16.2.9.2 
Physical Examination 
16.2.9.3 
Prior and Concomitant Medications  
16.2.9.4 
Prior and Concomitant Therapy and Procedures 
 
 
 
Confidential 
 
Page 37 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX B: TABLE LAYOUTS 
 
 
Confidential 
 
Page 38 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.1.1.1 
Subject Disposition 
All Randomized Subjects 
 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
Total 
(N= ) 
 
 
 
 
 
 
All Randomized 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  Study Medication not Dispensed 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Safety Population[1] 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
mITT Population[2] 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
PP Population[3] 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
Completed Study[4] 
 
 
 
 
 
Yes 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
No 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Primary reason for Discontinuation 
 
 
 
 
 
Adverse Event 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Withdrawal by Subject 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Physician Decision 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Protocol Violation 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Lost to Follow-Up 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Death 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Pregnancy 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Worsening Condition 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Lack of Efficacy 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Study Terminated by Sponsor 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Other 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviations: GSP, gravimetrically measured sweat production; mITT, Intent-to-Treat; PP, Per-Protocol 
 
[1] Safety Population includes all subjects randomized in the study who received study drug at least once. Treatment group assignment is based on the treatment actually received. 
[2] mITT Population includes all subjects who were randomized and dispensed study drug. Treatment group assignment is based on the planned treatment assignment. 
[3] PP Population includes all Safety subjects who meet all inclusion/exclusion criteria, have not taken/applied any interfering concomitant medications, and have full data collected for all GSP visits. 
[3] Defined as a disposition term of “Normal Study Completion”. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
0BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 39 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.1.1.2 
Subject Disposition by Study Center 
All Randomized Subjects 
 
 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
Total 
(N= ) 
 
 
 
 
 
 
 
Site 1 
All Randomized 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  Study Medication not Dispensed 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Safety Population[1] 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
mITT Population[2] 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
PP Population[3] 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
Completed Study 
 
 
 
 
 
 
Yes 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
No 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Study Medication not Dispensed 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
Primary reason for Discontinuation 
 
 
 
 
 
 
Adverse Event 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Withdrawal by Subject 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Physician Decision 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Protocol Violation 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Lost to Follow-Up 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Death 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Pregnancy 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Worsening Condition 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Lack of Efficacy 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Study Terminated by Sponsor 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Other 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
Site 2 
… 
 
 
 
 
 
 
Abbreviations: mITT, Intent-to-Treat; PP, Per-Protocol 
 
[1] Safety population includes all subjects randomized in the study who received study drug at least once. Treatment group assignment is based on the treatment actually received. 
[2] mITT population includes all subjects who were randomized and dispensed study drug. Treatment group assignment is based on the planned treatment assignment. 
[3] PP population includes all Safety subjects who meet all inclusion/exclusion criteria, have not taken/applied any interfering concomitant medications, and have full data collected for all GSP visits. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 40 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 
Table 14.1.2 
Major Protocol Violations 
Safety Population 
 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
Total 
(N= ) 
 
 
 
 
 
 
Any Major Protocol Violations 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Violation Category #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Violation Category #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects reporting more than one violation in a category are counted only once and subjects may be included in more than one category.  
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 41 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.1.3.1 
Demographics 
Safety Population 
 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
Total 
(N= ) 
 
 
 
 
 
 
Age 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x 
x 
x 
x 
x 
Min, Max 
x, x 
x, x 
x, x 
x, x 
x, x 
 
 
 
 
 
 
Sex 
 
 
 
 
 
Male 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Female 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
Hispanic or Latino 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Not Hispanic or Latino 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
Race[1] 
 
 
 
 
 
American Indian or Alaska Native 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Asian 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Black or African American 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Native Hawaiian or Other Pacific Islander 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
White 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Other 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
[1] Subjects reporting more than one race are included in all relevant race categories. Percentages will add up to >100%. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: 
• 
Repeat for the following:  
Table 14.1.3.2 
Demographics (mITT Population) 
Table 14.1.3.3 
Demographics (PP Population);  
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft 
BBI-4000-CL-203 
 
Page x of y 
 
Confidential 
 
Page 42 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.1.4.1 
Baseline Characteristics 
Safety Population 
 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
Total 
(N= ) 
 
 
 
 
 
 
Height (cm) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
Min, Max 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
 
 
 
 
 
Weight (kg) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
Min, Max 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
 
 
 
 
 
BMI (kg/m2) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
Min, Max 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
 
 
 
 
 
Time Since Start of Axillary Hyperhidrosis 
Symptoms (Months)[1] 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
Min, Max 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
Abbreviations: BMI, body mass index 
 
[1] Time since start of axillary hyperhidrosis symptoms is calculated as date informed consent signed – start date of axillary hyperhidrosis symptoms. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Repeat as Table 14.1.4.2 
Baseline Characteristics, mITT Population 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 43 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.1.5 
Medical History 
Safety Population 
 
System Organ Class[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
Total 
(N= ) 
 
 
 
 
 
 
Subjects Reporting any Medical History 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 
Body System #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Body System #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects reporting more than one medical history event for a given body system are counted only once. 
 
[1] Medical history events are coded to system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 44 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.1.6 
Prior Medications 
Safety Population 
 
ATC Class / 
Generic Drug Name 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects Receiving any Prior Medications 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
ATC Class #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
. 
 
 
 
 
. 
 
 
 
 
 
 
 
 
ATC Class #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
. 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
Abbreviations: ATC, anatomic therapeutic chemical, WHO, World Health Organization 
 
Notes: 
• 
Prior medications are those medications received prior to the first dose of study drug. 
• 
Medications are coded to ATC drug class (level 4) and generic drug names using the WHO Drug dictionary enhanced, version B2 March 1, 2016. 
• 
At each level of summarization (any medication, ATC class, generic drug name), subjects reporting use of more than one medication are counted only once. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes:  
• 
Sort medications by descending order of ATC class incidence and by descending order of drug name incidence within ATC class, based on the overall incidence (i.e., 
sum over all treatment groups). 
• 
When creating ATC level 4 drug class, utilize level 3 term if level 4 is missing in dataset and level 2 if both level 3 and level 4 are missing in the dataset 
• 
Repeat as Table 14.1.7 
Prior Therapy and Procedures 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203   
 
Page x of y
 
Confidential 
 
Page 45 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.1.1 
HDSM-Ax Summary of First and Last Visits 
mITT Population 
 
Study Day/s with Non-Missing Data 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects with Data: 
 
 
 
 
 At Visit 1 and Visit 4 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Visit 1 Only 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Visit 4 Only 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Missing Visit 1 and Visit 4 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
Last Study Visit Data at 
 
 
 
 
 Day 8 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 15 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 22 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 29 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 36 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 41 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 42 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 57 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
Subjects with Data:  
 
 
 
 
 At Day 41 and Day 42 and Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Any 2 of Days 41, 42, or 43  
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Any 1 of Days 41, 42, or 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Missing data at Days 41, 42, and 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviation: HDSM-Ax, Hyperhidrosis Disease Severity Measure-Axillary 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Repeat for Table 14.2.1.2 
HDSM-Ax Summary of First and Last Visits (PP Population) 
 
                       
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203   
 
Page x of y
 
Confidential 
 
Page 46 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.1.3 
HDSM-Ax End of Therapy Change from Baseline ANCOVA  
mITT Population 
 
Abbreviations: ANCOVA, analysis of covariance; HDSM-Ax, Hyperhidrosis Disease Severity Measure-Axillary; mITT, Intent-to-Treat; LSM, Least Square Mean; LSMD Least Square 
Mean Difference 
 
[1] Baseline is defined as the average of any available Visit 1 (Screening) and Visit 4 (Rescreening) values.  
[2] End of Therapy is defined as the average of any available Day 41, Day 42, and Day 43 values. 
[3] End of Therapy Imputed includes subjects missing all end of therapy values, where data is imputed by the last three available post-baseline visits. 
[4] P-values comparing active dose to vehicle are based on an ANCOVA model with covariate adjustment for the baseline value. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for End of Therapy Imputed [3], and BBI -4000 Doses (10%, 15%). Repeat for Table 14.2.1.4 
HDSM-Ax End of Therapy Change from Baseline ANCOVA 
(PP Population) 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
Time Point 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
Observed Value 
Change from Baseline % Change from Baseline  Observed Value 
Change from Baseline 
% Change from Baseline 
 
 
 
 
 
 
 
Baseline[1] 
 
 
 
 
 
 
 
n 
n 
 
 
 
n 
 
 
Mean (SD) 
x.x (x.xx) 
 
 
 
x.x (x.xx) 
 
 
Median 
x.x 
 
 
 
x.x 
 
 
Min, Max 
x.x, x.x 
 
 
 
x.x, x.x 
 
 
 
 
 
 
 
 
 
End of Therapy[2] 
 
 
 
 
 
 
 
n 
n 
n 
n 
 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x.x 
x.x 
x.x 
 
x.x 
x.x 
x.x 
Min, Max 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
 
 
 
 
 
 
 
LSM (SE) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
LSMD (active dose – vehicle) (SE) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
95% CI of LSMD 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
xx.x, xx.x 
xx.x, xx.x 
   ANCOVA p-value[4] 
 
 
 
 
 
x.xxxx 
x.xxxx 
 
 
 
 
 
 
 
…. 
 
 
 
 
 
 
 
 
Confidential 
 
Page 47 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.1.5 
HDSM-Ax Change from Baseline MMRM and Change from Baseline by Visit ANCOVA  
mITT Population 
 
Abbreviations: ANCOVA, analysis of covariance; HDSM-Ax, Hyperhidrosis Disease Severity Measure-Axillary; mITT, Intent-to-Treat; MMRM, mixed model for repeated measures; 
LSM, Least Square Mean; LSMD Least Square Mean Difference 
 
[1] Baseline is defined as the average of any available Visit 1 (Screening) and Visit 4 (Rescreening) values.  
 [2] P-values comparing active dose to vehicle are based on an ANCOVA model with covariate adjustment for the baseline value. 
[3] P-value comparing active dose to vehicle are based on an MMRM with subject as a random effect, treatment, protocol-specified visit, baseline, and baseline*visit interaction as fixed effects. 
[4] P-value is for the collective treatment*visit interaction based on an MMRM with subject as a random effect, and treatment, protocol-specified visit, treatment*visit interaction, baseline, and 
baseline*visit interactions as fixed effects.  
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Table continues on next page. 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
Time Point 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
Observed Value Change from Baseline % Change from Baseline  Observed Value 
Change from Baseline 
% Change from Baseline 
 
 
 
 
 
 
 
Baseline[1] 
 
 
 
 
 
 
 
n 
n 
 
 
 
n 
 
 
Mean (SD) 
x.x (x.xx) 
 
 
 
x.x (x.xx) 
 
 
Median 
x.x 
 
 
 
x.x 
 
 
Min, Max 
x.x, x.x 
 
 
 
x.x, x.x 
 
 
    
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
…. 
 
 
 
 
 
 
   LSM (SE) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
LSMD (active dose – vehicle) (SE) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
95% CI of LSMD 
 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
ANCOVA p-value[2] 
 
 
 
 
x.xxxx 
x.xxxx 
…. 
 
 
 
 
 
 
MMRM treatment p-value[3] 
 
 
 
 
 
x.xxxx 
x.xxxx 
MMRM treatment*visit p-value[4] 
 
 
 
 
x.xxxx 
x.xxxx 
 
Confidential 
 
Page 48 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
• 
Continue for Day 8 summary statistics (n, Mean (SD), Median, and Min, Max). 
• 
Continue for Days 15, 22, 29, 36, and 57, each visit to include summary statistics.  
• 
Continue for remaining BBI -4000 Doses (10%, 15%).  
• 
For Days 8, 15, 22, 29, 36, 41-43, and 57 include ANCOVA p-value for each visit.  
• 
For MMRM analyses, use data on Days 8, 15, 22, 29, 36 and End of Therapy.  
• 
MMRM p-values are not associated with any visit Day. Show treatment and treatment*visit p-values once at bottom of each treatment group. 
• 
Repeat for Table 14.2.1..6 
HDSM-Ax Change from Baseline MMRM and Change from Baseline by Visit ANCOVA (PP Population) 
 
 
 
Confidential 
 
Page 49 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.2.1.7 
HDSM-Ax Responder MMRM   
mITT Population 
 
HDSM-Ax Parameter 
Time Point 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
n (%) 
 
n (%) 
P-value[1] 
Reduction from Baseline[2] >1 
Day 8 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
Day 15 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
Day 22 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
Day 29 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
Day 36 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
…. 
 
 
 
 
End of Therapy[3] 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
 
 
 
 
MMRM treatment p-value[4] 
 
 
 
x.xxxx 
MMRM treatment*visit p-value[5] 
 
 
 
x.xxxx 
 
 
 
 
Reduction from Baseline[2] >2 
… 
 
 
 
 
 
Abbreviations: HDSM-Ax, Hyperhidrosis Disease Severity Measure-Axillary; mITT, Intent-to-Treat; MMRM, mixed model for repeated measures 
 
Note: Responder is defined as a subject who achieved the reduction in HDSM-Ax score specified in the HDSM-Ax Parameter column, between Baseline and End of Therapy. Subjects without a 
defined improvement in score are considered non-responders. 
 
[1] P-values comparing active treatment to vehicle are based on a binary logistic regression model where treatment and baseline HDSM-Ax Score are predictors. 
[2] Baseline is defined as the average of any available Visit 1 (Screening) and Visit 4 (Rescreening) values. 
[3] End of Therapy is defined as the average of any available Day 41, Day 42, and Day 43 values. 
[4] P-values comparing active dose to vehicle are based on an MMRM with subject as a random effect, treatment, protocol-specified visit, baseline, and baseline*visit interaction as fixed effects. 
[5] P-value is for the collective treatment*visit interactions based on an MMRM with subject as a random effect, and treatment, protocol-specified visit, treatment*visit interaction, baseline, and 
baseline*visit interactions as fixed effects. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for Days 41, 42, 43, 57, HDSM-Ax >2, and remaining BBI-4000 dose groups (10%, 15%). Repeat as Table 14.2.1.8 HDSM-Ax Responder MMRM (PP Population).  
MMRM = generalized linear mixed model for repeated measures, with logit linkage. For MMRM .analyses, use data on Days 8, 15, 22, 29, 36 and End of Therapy. 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 50 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.2.1 
HDSM-Ax and GSP Responder MMRM 
mITT Population 
 
HDSM-Ax and GSP Parameters 
Time Point 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
n (%) 
 
n (%) 
P-value[1] 
 
 
 
 
HDSM-Ax reduction from Baseline[2] >1 and GSP reduction from Baseline[2] ≥ 50% 
Day 8 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
Day 15 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
Day 22 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
…. 
 
 
 
 
End of Therapy[3] 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
 
 
 
 
MMRM treatment p-value[4] 
 
 
 
x.xxxx 
MMRM treatment*visit p-value[5] 
 
 
 
x.xxxx 
 
 
 
 
HDSM-Ax reduction from Baseline[2] >2 and GSP reduction from Baseline[2] ≥ 50% 
 
 
 
 
…. 
 
 
 
 
 
Abbreviations: GSP, gravimetrically measured sweat production; HDSM-Ax, Hyperhidrosis Disease Severity Measure-Axillary; mITT, Intent-to-Treat; MMRM, mixed model for repeated measures 
 
Note: Responder is defined as a subject who achieved the reduction in HDSM-Ax score specified in the HDSM-Ax Parameter column, between Baseline and End of Therapy. Subjects without a 
defined improvement in score are considered non-responders. 
 
[1] P-values comparing active treatment to vehicle are based on a binary logistic regression model where treatment and baseline HDSM-Ax Score are predictors. 
[2] HDSM-Ax baseline is defined as the average of any available Visit 1 (Screening) and Visit 4 (Rescreening) values; GSP baseline is defined as the median of any available GSP measurements from 
Visit 2, Visit 3, and Visit 4. 
[3] HDSM-Ax End of Therapy is defined as the average any available Day 41, Day 42, and Day 43 values; GSP End of Therapy is defined as the median of any available GSP measurements from Day 
41, Day 42, and Day 43. 
[4] P-values comparing active dose to vehicle are based on an MMRM with subject as a random effect, treatment, protocol-specified visit, baseline, and baseline*visit interaction as fixed effects. 
[5] P-value is for the collective treatment*visit interactions based on an MMRM with subject as a random effect, and treatment, protocol-specified visit, treatment*visit interaction, baseline, and 
baseline*visit interactions as fixed effects. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for Days 29, 36, 41, 42, 43, 57, HDSM-Ax >2, and remaining BBI-4000 dose groups (10%, 15%); Repeat as Table 14.2.2.2 
HDSM-Ax and GSP Responder MMRM 
(PP Population).  MMRM = generalized linear mixed model for repeated measures, with logit linkage. For MMRM analyses, use data on Days 8, 15, 22, 29, 36 and End of Therapy. 
 
   Brickell Biotech, Inc. 
  Database Date/Analysis: DDMMMYYYY/Draft
   BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 51 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.3.1 
GSP Summary of First and Last Visits 
mITT Population 
 
Study Day/s with Non-Missing Data 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects with Data: 
 
 
 
 
 At Visit 1 and Visit 4 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Visit 1 Only 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Visit 4 Only 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Missing Visit 1 and Visit 4 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
Last Study Visit Data at 
 
 
 
 
 Day 8 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 15 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 22 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 29 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 36 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 41 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 42 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 57 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
Subjects with Data:  
 
 
 
 
 At Day 41 and Day 42 and Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Any 2 of Days 41, 42, or 43  
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Any 1 of Days 41, 42, or 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Missing data at Days 41, 42, and 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviations: GSP, gravimetrically measured sweat production; mITT, Intent-to-Treat 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Repeat as Table 14.2.3.2 
 
GSP Summary of First and Last Visits (PP Population) 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203   
 
Page x of y
 
Confidential 
 
Page 52 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.3.3 
Summary of Missing Singular Axilla GSP Measurements 
mITT Population 
 
Study Day/s with GSP data missing from a single axilla 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects missing GSP data from a single axilla: 
 
 
 
 
 At Any Visit 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 GSP 1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 GSP 2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 GSP 3 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
 Day 8 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 15 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 22 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 29 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 36 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 41 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 42 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 57 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviations: GSP, gravimetrically measured sweat production; mITT, Intent-to-Treat 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Repeat as Table 14.2.3.4 
 
Summary of Missing Singular Axilla GSP Measurements (PP Population) 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203   
 
Page x of y
 
Confidential 
 
Page 53 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.3.5 
GSP End of Therapy Change from Baseline ANCOVA  
mITT Population 
 
Abbreviations: ANCOVA, analysis of covariance; GSP, gravimetrically measured sweat production; mITT, Intent-to-Treat; LSM, Least Square Mean; LSMD Least Square Mean Difference 
 
[1] Method of calculating average for Baseline, End of Therapy, and End of Therapy Imputed. 
[2] Baseline is defined as the median/mean of any available Visit 2, Visit 3, and Visit 4 values. 
[3] End of Therapy is defined as the median/mean of any available Day 41, Day 42, and Day 43 values. 
[4] End of Therapy Imputed includes subjects missing all end of therapy values, where data is imputed by the median/mean of the last three available post-baseline visits. 
[5] P-values comparing active dose to vehicle are based on an ANCOVA model with covariate adjustment for the baseline value. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Table continues on next page. 
 
Brickell Biotech, Inc. 
  Database Date/Analysis: DDMMMYYYY/Draft 
BBI-4000-CL-203   
 
Page x of y 
Time Point 
Type of 
Average[1] 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
Observed Value Change from Baseline % Change from Baseline  Observed Value Change from Baseline % Change from Baseline 
 
 
 
 
 
 
 
 
Baseline[2] 
Median 
 
 
 
 
 
 
 
n 
 
n 
 
 
 
n 
 
 
Mean (SD) 
 
x.x (x.xx) 
 
 
 
x.x (x.xx) 
 
 
Median 
 
x.x 
 
 
 
x.x 
 
 
Min, Max 
 
x.x, x.x 
 
 
 
x.x, x.x 
 
 
 
 
 
 
 
 
 
 
 
End of Therapy[3] 
 
 
 
 
 
 
 
 
n 
 
n 
n 
n 
 
n 
n 
n 
Mean (SD) 
 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
 
x.x 
x.x 
x.x 
 
x.x 
x.x 
x.x 
Min, Max 
 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
x.x, x.x 
x.x, x.x 
x.x, x.x 
 
 
 
 
 
 
 
 
LSM (SE) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
LSMD (active dose – vehicle) (SE) 
 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
95% CI of LSMD 
 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
xx.x, xx.x 
xx.x, xx.x 
  ANCOVA p-value[5] 
 
 
 
 
 
 
x.xxxx 
x.xxxx 
…. 
 
 
 
 
 
 
 
 
 
Confidential 
 
Page 54 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
• 
Continue for End of Therapy Imputed [4], BBI -4000 Doses (10%, 15%), and repeat using mean method for calculating Baseline, EoT and EoT Imputed.  
• 
Repeat for Table 14.2.3.6 
GSP End of Therapy Change from Baseline ANCOVA (PP Population) 
• 
For ranked values, rank continuous data low-to-high within each visit, disregarding treatment. 
• 
Repeat for Table 14.2.3.7 
GSP End of Therapy Change from Baseline ANCOVA for Ranked Values (mITT Population) 
• 
Repeat for Table 14.2.3.8 
GSP End of Therapy Change from Baseline ANCOVA for Ranked Values  (PP Population) 
 
 
 
Confidential 
 
Page 55 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.2.3.9 
GSP Change from Baseline MMRM and Change from Baseline by Visit ANCOVA  
mITT Population 
 
Abbreviations: ANCOVA, analysis of covariance; GSP, gravimetrically measured sweat production; mITT, Intent-to-Treat; MMRM, mixed model for repeated measures; LSM, Least 
Square Mean; LSMD Least Square Mean Difference 
 
[1] Method of calculating average for Baseline and End of Therapy. 
[2] Baseline is defined as the median/mean of any available Visit 2, Visit 3, and Visit 4 values. 
[3] P-values comparing active dose to vehicle are based on an ANCOVA model with covariate adjustment for the baseline value. 
[4] P-value comparing active dose to vehicle are based on an MMRM with subject as a random effect, treatment, protocol-specified visit, baseline, and baseline*visit interaction as fixed effects. 
[5] P-value is for the collective treatment*visit interactions based on an MMRM with subject as a random effect, and treatment, protocol-specified visit, treatment*visit interaction, baseline, and 
baseline*visit interactions as fixed effects.   
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Table continues on next page. 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
Time Point 
Type of 
Average[1] 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
Observed Value Change from Baseline % Change from Baseline  Observed Value Change from Baseline % Change from Baseline 
 
 
 
 
 
 
 
 
Baseline[2] 
Median 
 
 
 
 
 
 
 
n 
 
n 
 
 
 
n 
 
 
Mean (SD) 
 
x.x (x.xx) 
 
 
 
x.x (x.xx) 
 
 
Median 
 
x.x 
 
 
 
x.x 
 
 
Min, Max 
 
x.x, x.x 
 
 
 
x.x, x.x 
 
 
   
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
   …. 
 
 
 
 
 
 
 
LSM (SE) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
LSMD (active dose – vehicle) (SE) 
 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
95% CI of LSMD 
 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
xx.x, xx.x 
xx.x, xx.x 
  ANCOVA p-value[3] 
 
 
 
 
 
 
x.xxxx 
x.xxxx 
…. 
 
 
 
 
 
 
 
 
MMRM treatment p-value[4] 
 
 
 
 
 
 
x.xxxx 
x.xxxx 
MMRM treatment*visit p-value[5] 
 
 
 
 
 
 
x.xxxx 
x.xxxx 
 
Confidential 
 
Page 56 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
• 
Continue for Day 8 summary statistics (n, Mean (SD), Median, and Min, Max). 
• 
Continue for Days 15, 22, 29, 36, and 57, each visit to include summary statistics.  
• 
Continue for remaining BBI -4000 Doses (10%, 15%).  
• 
For Days 8, 15, 22, 29, 36, 41-43, and 57 include ANCOVA p-value for each visit.  
• 
For MMRM analyses, use data on Days 8, 15, 22, 29, 36 and End of Therapy. 
• 
MMRM p-values are not associated with any visit Day. Show treatment and treatment*visit p-values once at bottom of page for each treatment group. 
• 
Repeat analyses with mean method for calculating Baseline and EoT.  
• 
Repeat for Table 14.2.3.10 
 
GSP Change from Baseline MMRM and Change from Baseline by Visit ANCOVA (PP Population) 
• 
Repeat tables with ranked values. Rank continuous data low-to-high within each visit, disregarding treatment, and use average for ties. 
• 
Repeat for Table 14.2.3.11 
 
GSP Change from Baseline MMRM and Change from Baseline by Visit ANCOVA for Ranked Values (mITT Population) 
• 
Repeat for Table 14.2.3.12 
 
GSP Change from Baseline MMRM and Change from Baseline by Visit ANCOVA for Ranked Values (PP Population 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidential 
 
Page 57 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.2.3.13 
GSP Responder MMRM   
mITT Population 
 
Time Point 
Type of 
Average[1] 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
n (%) 
 
n (%) 
P-value[2] 
 
n (%) 
P-value[2] 
 
n (%) 
P-value[2] 
Day 8 
Median 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 15 
 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 22 
 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
…. 
 
 
 
 
 
 
 
 
 
 
 
End of Therapy[3] 
 
n (x.x%) 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
 
 
 
 
 
 
 
 
 
 
MMRM treatment p-value[4] 
 
 
 
 
x.xxxx 
 
 
x.xxxx 
 
 
x.xxxx 
MMRM treatment*visit p-value[5] 
 
 
 
 
x.xxxx 
 
 
x.xxxx 
 
 
x.xxxx 
 
Abbreviations: GSP, gravimetrically measured sweat production; mITT, Intent-to-Treat; MMRM, mixed model for repeated measures 
 
Note: Responder is defined as a subject who achieved a reduction in GSP of at least 50% between Baseline and End of Therapy. Subjects without a defined improvement in score are considered non-
responders. 
 
[1] Method of calculating average for Baseline and End of Therapy. 
[2] P-values comparing active treatment to vehicle are based on a binary logistic regression model where treatment and baseline GSP are predictors. 
[3] End of Therapy is defined as the median/mean of any available Day 41, Day 42, and Day 43 values. 
[4] P-values comparing active dose to vehicle are based on a logit-linked MMRM with subject as a random effect, treatment, protocol-specified visit, baseline, and baseline*visit interaction as fixed 
effects. 
[5] P-value is for the collective treatment*visit interactions based on a logit-linked MMRM with subject as a random effect, and treatment, protocol-specified visit, treatment*visit interaction, baseline, 
and baseline*visit interactions as fixed effects. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes:  
• 
Continue for Days 29, 33, 41, 42, 43, 57. Repeat analysis with mean method for calculating Baseline and EoT. 
• 
MMRM = generalized linear mixed model for repeated measures, with logit linkage.  
• 
For MMRM analyses, use data on Days 8, 15, 22, 29, 36 and End of Therapy. 
• 
Repeat as Table 14.2.3.14 
GSP Responder MMRM (PP Population).   
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203      
 
 Page x of y
 
Confidential 
 
Page 58 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.2.4.1 
HDSS Summary of First and Last Visits 
mITT Population 
 
Study Day/s with Non-Missing Data 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects with Data: 
 
 
 
 
 At Visit 1 and Visit 4 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Visit 1 Only 
 
 
 
 
 At Visit 4 Only 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Missing Visit 1 and Visit 4 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Last Study Visit Data at 
 
 
 
 
 Day 8 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 15 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 22 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 29 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 36 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 41 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 42 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Day 57 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
Subjects with Data:  
 
 
 
 
 At Day 41 and Day 42 and Day 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Any 2 of Days 41, 42, or 43  
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 At Any 1 of Days 41, 42, or 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 Missing data at Days 41, 42, and 43 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviations: HDSS, Hyperhidrosis Disease Severity Scale; mITT, Intent-to-Treat 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Repeat as Table 14.2.4.2 
 
HDSS Summary of First and Last Visits (PP Population) 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft 
BBI-4000-CL-203   
 
Page x of y 
 
Confidential 
 
Page 59 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.2.4.3 
HDSS Responder Regression 
mITT Population 
 
HDSS Parameter 
Time Point 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
n (%) 
P-value[1] 
 
n (%) 
P-value[1] 
 
n (%) 
P-value[1] 
 
n (%) 
P-value[1] 
 
 
 
 
 
 
 
 
 
 
 
Change from 
Baseline≥1 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 15 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 22 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 29 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 36 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 41 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 42 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 43 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
End of Therapy[3] 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
Day 57 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
n (x.x%) 
x.xxxx 
 
 
 
 
 
 
 
 
 
 
 
Change from Baseline 
≥2 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: HDSS, Hyperhidrosis Disease Severity Scale; mITT, Intent-to-Treat 
 
Note: Responder is defined as a subject who achieved a reduction in HDSS score specified in the Parameter column, between Baseline and End of Therapy. Subjects without a defined improvement in 
score are considered non-responders. 
 
[1] P-values comparing active treatment to vehicle are based on a binary logistic regression where treatment and baseline HDSS score are predictors. 
[2] Baseline is defined as the average of any available Visit 1 (Screening) and Visit 4 (Rescreening) values. 
[3] End of Therapy is defined as the average of any available Day 41, Day 42, and Day 43 values. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for Change from Baseline >2. Repeat as Table 14.2.4.4  
HDSS Responder Regression (PP Population) 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft 
 BBI-4000-CL-203   
 
Page x of y 
 
Confidential 
 
Page 60 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 
Table 14.2.5.1 
DLQI Change Score ANCOVA 
mITT Population 
 
 
Abbreviations: ANCOVA, analysis of covariance; DLQI, Dermatology Life Quality Index; mITT, Intent-to-Treat; LSM, Least Square Mean; LSMD Least Square Mean Difference 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
[2] P-values comparing active dose to vehicle are based on an ANCOVA model for change scores, with covariate adjustment for the baseline value. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Repeat for Table 14.2.5.2 
DLQI Change Score ANCOVA (PP Population) 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
Time Point 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
Observed Value 
Change from 
Baseline 
 Observed Value 
Change from 
Baseline 
 
Observed Value 
Change from 
Baseline 
 
Observed Value 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
 
 
n 
 
 
n 
 
 
n 
 
Mean (SD) 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
Median 
x.x 
 
 
x.x 
 
 
x.x 
 
 
x.x 
 
Min, Max 
x.x, x.x 
 
 
x.x, x.x 
 
 
x.x, x.x 
 
 
x.x, x.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
n 
 
n 
n 
 
n 
n 
 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
Median 
x.x 
x.x 
 
x.x 
x.x 
 
x.x 
x.x 
 
x.x 
x.x 
Min, Max 
x.x, x.x 
x.x, x.x 
 
x.x, x.x 
x.x, x.x 
 
x.x, x.x 
x.x, x.x 
 
x.x, x.x 
x.x, x.x 
 
 
 
 
 
 
 
 
 
 
 
 
LSM (SE) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
xx.x (xx.xx) 
LSMD (active dose – vehicle) (SE) 
 
xx.x (xx.xx) 
 
 
xx.x (xx.xx) 
 
 
xx.x (xx.xx) 
 
 
xx.x (xx.xx) 
95% CI of LSMD 
 
xx.x, xx.x 
 
 
xx.x, xx.x 
 
 
xx.x, xx.x 
 
 
xx.x, xx.x 
ANCOVA p-value[2] 
 
 
 
 
x.xxxx 
 
 
x.xxxx 
 
 
x.xxxx 
 
Confidential 
 
Page 61 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 
Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety Population 
Part 1 of 2 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
Total Number of TEAEs 
xx 
xx 
xx 
xx 
Total Number of TESAEs 
xx 
xx 
xx 
xx 
 
 
 
 
 
Number (%) of Subjects Reporting at Least One: 
 
 
 
 
TEAE 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE by Severity[1] 
 
 
 
 
Mild 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Moderate 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Severe 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE by Relationship[2] 
 
 
 
 
Not Related 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Related 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE Leading to Discontinuation of Study Drug 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE Requiring Dose Interruption of Study Drug 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE Requiring Dose Reduction of Study Drug 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE Leading to Premature Withdrawal from the Study 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TEAE Causing Death 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Treatment Area 
 
 
 
 
TEAE in Treatment Area? 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviations: SAE, serious adverse event; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event 
 
[1] Subjects reporting more than one adverse event are counted only once using the highest severity. 
[2] Subjects reporting more than one adverse event are counted only once using the closest relationship to study drug. Not related events includes those reported as “Unlikely” or “Not Related” to study 
drug; related events include those reported as “Possibly Related,” “Probably Related,” or “Definitely Related” to study drug. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Table continues on next page. 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft 
BBI-4000-CL-203   
 
Page x of y 
 
Confidential 
 
Page 62 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety Population 
Part 2 of 2 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
TESAE 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TESAE by Severity[1] 
 
 
 
 
Mild 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Moderate 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Severe 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
TESAE by Relationship[2] 
 
 
 
 
Not Related 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Related 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Treatment Area 
 
 
 
 
TESAE in Treatment Area? 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Abbreviations: SAE, serious adverse event; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event 
 
[1] Subjects reporting more than one adverse event are counted only once using the highest severity. 
[2] Subjects reporting more than one adverse event are counted only once using the closest relationship to study drug. Not related events includes those reported as “Unlikely” or “Not Related” to study 
drug; related events include those reported as “Possibly Related,” “Probably Related,” or “Definitely Related” to study drug. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 63 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class /  
  Preferred Term[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
System Organ Class #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
System Organ Class #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
Note: At each level of summarization (any event, system organ class, and preferred term), subjects reporting more than one adverse event are counted only once. 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Sort events by descending order of system organ class incidence and by descending order of preferred term incidence within system organ class, based on the overall incidence 
(i.e., sum over all treatment groups). 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.3 
 
Most Frequently-Occurring (≥ 10% Overall) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class /  
  Preferred Term[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
System Organ Class #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  … 
 
 
 
 
 
 
 
 
System Organ Class #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
  … 
 
 
 
 
 
 
 
 
 
Note: Subjects reporting more than one adverse event are counted only once. Summary includes all events reported by ≥ 10% of subjects in the Safety Population. 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Sort events by descending order of SOC term incidence, preferred term incidence, based on the overall incidence (i.e., sum over all treatment groups). 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 65 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.4 
 
Treatment-Emergent Adverse Events Related to Study Drug by Preferred Term 
Safety Population 
 
Preferred Term[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #3 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
Note: Subjects reporting more than one related adverse event are counted only once. Summary includes all related events (i.e., “Possibly Related,” “Probably Related,” or “Definitely Related” to study 
drug). 
 
[1] Adverse events are coded to preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Sort events by descending order of preferred term incidence, based on the overall incidence (i.e., sum over all treatment groups 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 66 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.5 
Treatment-Emergent Adverse Events by Severity, System Organ Class, and Preferred Term 
Safety Population 
 
System Organ Class / 
Preferred Term[1] 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
Mild 
Moderate 
Severe 
 
Mild 
Moderate Severe  
Mild 
Moderate 
Severe  
Mild 
Moderate 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class #1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
… 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class #2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
… 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: At each level of summarization (any event, system organ class, and preferred term), subjects reporting more than one adverse event are counted only once using the highest severity. 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Sort events by descending order of system organ class incidence, and preferred term incidence within system organ class, based on the overall incidence (ie, sum over all severity 
grades and treatment groups). 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.3.1.6 
Treatment-Emergent Adverse Events Related to Study Drug by Severity, System Organ Class, and Preferred Term 
Safety Population 
 
System Organ Class /  
  Preferred Term[1] 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
Mild 
Moderate 
Severe 
 
Mild 
Moderate 
Severe  
Mild 
Moderate 
Severe  
Mild 
Moderate 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Reporting at Least One Adverse Event 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class #1 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
   Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class #2 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: At each level of summarization (any event, system organ class, and preferred term), subjects reporting more than one related are counted only once using the highest severity. Related adverse 
events are those reported as “Possibly Related,” “Probably Related,” or “Definitely Related” to study drug. 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
Programming Note: Sort events by descending order of system organ class incidence and by descending order of preferred term incidence within system organ class, based on the overall incidence 
(i.e., sum over all treatment groups). 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
Page x of y
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.7 
Treatment-Emergent Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class /  
  Preferred Term[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subject Reporting at Least One Serious Adverse Event 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
System Organ Class #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
System Organ Class #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
Note: At each level of summarization (any event, system organ class, and preferred term), subjects reporting more than one serious adverse event are counted only once. 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Sort events by descending order of system organ class incidence and by descending order of preferred term incidence within system organ class, based on the overall incidence 
(i.e., sum over all treatment groups). 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 69 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.8 
 
Treatment-Emergent Serious Adverse Events Related to Study Drug by Preferred Term 
Safety Population 
 
Preferred Term[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Preferred Term #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Preferred Term #3 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
Note: Subjects reporting more than one related adverse event are counted only once. Summary includes all related events (i.e., “Possibly Related,” “Probably Related,” or “Definitely Related” to study 
drug). 
 
[1] Adverse events are coded to preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Sort events by descending order of preferred term incidence, based on the overall incidence (i.e., sum over all treatment groups 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 70 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.3.1.9 
Local Tolerability Assessments – Subject Assessments 
Safety Population 
 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
Baseline Assessment[1] 
Baseline Assessment[1] 
Parameter 
Visit 
Absent 
Minimal 
Mild 
Moderate 
Severe 
Missing 
 
Absent 
Minimal 
Mild 
Moderate 
Severe 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
Itching 
Day 8 
(n= ) 
 
 
 
 
 
 
(n= ) 
 
 
 
 
 
Absent 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Mild 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Moderate 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Severe 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Missing 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
Abbreviation: ET, early termination 
 
Notes:  
• 
Tolerability is assessed on a 5-point scale where 0= Absent, 1= Minimal, 2= Mild, 3= Moderate, 4= Severe. 
• 
Subjects self-evaluate Itching and Burning for each axilla prior to the Investigator’s evaluation. 
• 
Maximum severity assessed for either axilla is reported. 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Continue for Days 15, 22, 29, 36, 43, and 57, parameter Burning, for all BBI-4000 doses (10%, 15%). 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.1.10 
Local Tolerability Assessments – Investigator Assessments 
Safety Population 
 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
Baseline Assessment[1] 
 
Baseline Assessment[1] 
 
Parameter 
Visit 
Absent 
Mild 
Moderate 
Severe 
Missing 
 
Absent 
Mild 
Moderate 
Severe 
Missing 
 
 
 
 
 
 
 
 
 
 
 
Dryness 
Day 8 
(n= ) 
 
 
 
 
 
(n= ) 
 
 
 
 
Absent 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Mild 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Moderate 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Severe 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
Missing 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
Abbreviation: ET, early termination 
 
Notes:  
• 
Tolerability is assessed on a 5-point scale where 0= Absent, 1= Minimal, 2= Mild, 3= Moderate, 5= Severe. 
• 
Investigators evaluate Dryness, Scaling, and Erythema for each axilla after the Subject’s evaluation. 
• 
Maximum severity assessed at either axilla is reported. 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Continue for Days 15, 22, 29, 36, 43, and 57, parameters Scaling and Erythema, and BBI-4000 doses (10%, 15%) 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 72 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.2.1 
Listing of Deaths 
Safety Population 
 
Subject ID 
Treatment Group 
Date of Death (Study Day[1]) 
Cause of Death 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15%  
ddMMMyyyy (xx) 
Adverse event or cause of death from the study exit form 
xxx-xxxx 
 
 
 
… 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 73 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.2.2 
Listing of Serious Adverse Events 
Safety Population 
 
Subject 
ID 
Treatment 
Group 
System Organ Class[1] / 
Preferred Term[1] / 
Event Name 
In the 
Treatment 
Area? 
Start Date  
(Study 
Day[2]) 
End Date 
(Study Day[2]) Serious Criteria 
Severity 
Relationship to  
Study Drug 
Action Taken with 
Study Treatment 
Action Taken to  
Treat Event 
Outcome 
 
 
 
 
 
 
 
 
 
 
xxx-
xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
System Organ Class / 
Preferred Term / 
Event Name 
Yes / 
No 
ddMMMyyy
y (xx) 
ddMMMyyyy 
(xx) / 
Ongoing 
Congenital Anomaly 
or Birth Defect / 
Persistent or 
significant Disability / 
Death / 
Inpatient or Prolonged 
Hospitalization / 
Life Threatening / 
Other Serious or 
Important Medical 
Event 
Display all that are 
reported, separated by 
a comma 
Mild / 
Moderate 
/ 
Severe 
Not Related / 
Unlikely Related 
/ 
Possibly Related / 
Related 
None / 
Drug Interrupted / 
Drug Reduced / 
Drug Interrupted / 
Drug Withdrawn / 
Not Applicable / 
Unknown / 
Display all that 
are reported, 
separated by a 
comma 
None / 
Medication / 
Procedure or Therapy 
/ 
Hospitalization /  
Discontinued from 
Study / 
Other / 
Unknown  
Display all that are 
reported, separated by 
a comma 
Fatal / 
Not Recovered/Not 
Resolved/ 
Recovered/Resolved/ 
Recovered/Resolved 
with Sequelae / 
Recovering/Resolvin
g/ 
Unknown 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-
xxxx 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
[2] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.2.3 
Listing of Adverse Events Leading to Study Drug Discontinuation, Reduction or Interruption 
Safety Population 
 
 
Subject 
ID 
Treatment 
Group 
System Organ Class[1] / 
Preferred Term[1] / 
Event Name 
In the 
Treatment 
Area? 
 
Start Date  
(Study Day[2]) 
 
End Date 
(Study Day[2]) Serious Severity 
Relationship to  
Study Drug 
Action Taken with  
Study Treatment 
Action Taken to  
Treat Event 
Outcome 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10%/ 
BBI-4000 
15% 
System Organ Class / 
Preferred Term / 
Event Name 
Yes / 
No 
ddMMMyyyy 
(xx) 
ddMMMyyyy 
(xx) / 
Ongoing 
Yes / 
No 
Mild / 
Moderate / 
Severe 
Not Related / 
Unlikely Related / 
Possibly Related / 
Related 
None / 
Drug Interrupted / 
Drug Reduced / 
Drug Interrupted / 
Drug Withdrawn / 
Not Applicable / 
Unknown / 
Display all that are 
reported, separated 
by a comma 
None / 
Medication / 
Procedure or Therapy / 
Hospitalization /  
Discontinued from Study / 
Other / 
Unknown  
Display all that are 
reported, separated by a 
comma 
Fatal / 
Not Recovered/Not 
Resolved/ 
Recovered/Resolved
/ 
Recovered/Resolved 
with Sequelae / 
Recovering/Resolvi
ng/ 
Unknown 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Summary includes all adverse events where action taken is reported as “dose reduced,” “drug interrupted,” or “drug withdrawn.” 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
[2] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 75 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.4.1 
Listing of Abnormal Hematology Values 
Safety Population 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Test 
 
Unit 
 
Normal Range 
 
Result 
 
Alert 
Clinically 
Significant 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 5%/ 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy (xx) Test #1 
Unit 
xxx – xxx 
xxx 
Low / 
High 
Yes / 
null 
 
 
 
Test #2 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes:  
 
• 
Repeat as Table 14.3.4.2 
Listing of Abnormal Chemistry Values (Safety Population) 
• 
Repeat as Table 14.3.4.3 
Listing of Abnormal Urinalysis Values (Safety Population) 
 
 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.5.1 
Extent of Exposure 
Safety Population 
 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Duration of Exposure (days)[1] 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x 
x 
x 
x 
Min, Max 
x, x 
x, x 
x, x 
x, x 
 
 
 
 
 
[1] Duration of exposure to study treatment is calculated as the date of last dose of study drug – the date of first dose of study drug + 1. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.5.2 
Study Drug Compliance 
Safety Population 
 
Study Drug Compliance (%)[1] 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
x.x (x.xx) 
Median 
x 
x 
x 
x 
Min, Max 
x, x 
x, x 
x, x 
x, x 
 
 
 
 
< 80% Compliant 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
≥ 80% Compliant 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
[1] Study drug compliance is calculated as the number of doses received / the expected number of doses x 100. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.6.1 
Hematology – Univariate Summary by Parameter and Visit 
Safety Population 
 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
Parameter 
Visit 
Observed Value 
Change from 
Baseline 
 
Observed Value 
Change from 
Baseline 
 Observed Value  
Change from  
baseline 
 
Observed Value 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
RBC Count (1012/L) 
Baseline[1] 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
 
 
n 
 
 
n 
 
 
n 
 
Mean (SD) 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
Median 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
Min, Max 
x, x 
 
 
x, x 
 
 
x, x 
 
 
x, x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
n 
 
n 
n 
 
n 
n 
 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
Median 
x 
x 
 
x 
x 
 
x 
x 
 
x 
x 
 
Min, Max 
x, x 
x, x 
 
x, x 
x, x 
 
x, x 
x, x 
 
x, x 
x, x 
 
 
… 
Hematocrit (L/L) 
… 
 
Abbreviations: ET, early termination; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood cell; WBC, white 
blood cell 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for regularly-collected hematology parameters: Hemoglobin  (g/L), MCH (pg),  MCHC (g/L), MCV (fL),  Platelet Count (109/L),  WBC Count (109/L), Reticulocyte 
Count (109/L) Neutrophils (%), Lymphocytes (%),  Monocytes (%),  Eosinophils (%),  Basophils (%).  
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Table 14.3.6.2 
Hematology – Shift from Baseline to Worst Post-Baseline Value by Parameter 
Safety Population 
 
Parameter 
Worst Post-Baseline Assessment[2] 
Vehicle 
(N= ) 
Baseline Assessment[1] 
 
BBI-4000 5% 
(N= ) 
Baseline Assessment[1] 
 
BBI-4000 10% 
(N= ) 
Baseline Assessment[1] 
 
BBI-4000 15% 
(N= ) 
Baseline Assessment[1] 
Low 
Normal 
High 
 
Low 
Normal 
High 
 
Low 
Normal 
High 
 
Low 
Normal 
High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RBC Count 
 
(n=) 
 
 
 
(n=) 
 
 
 
(n=) 
 
 
 
(n=) 
 
 Low 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 Normal 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 High 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematocrit 
 
(n=) 
 
 
 
(n=) 
 
 
 
(n=) 
 
 
 
(n=) 
 
 Low 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 Normal 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 High 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemoglobin 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood cell; WBC, white blood cell 
 
Note: Percentages are based on the number of subjects with a non-missing baseline value and at least one non-missing post-baseline value (n=). 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
[2] The worst post-baseline assessment is defined as the value numerically farthest outside the normal range across all post-baseline visits through the end of the study. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Continue for regularly-collected hematology parameters: (MCH, MCHC, MCV, Platelet Count, WBC Count, Reticulocyte Count, Neutrophils, Lymphocytes Monocytes,   
Eosinophils,   Basophils 
 
 
 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.6.3 
Chemistry – Univariate Summary by Parameter and Visit 
Safety Population 
 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N= ) 
 
BBI-4000 10% 
(N= ) 
 
BBI-4000 15% 
(N= ) 
Parameter 
Visit 
Observed Value 
Change from 
Baseline 
 
Observed Value 
Change from 
Baseline 
 
Observed Value 
Change from 
Baseline 
 
Observed Value 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
AST (SGOT) 
(U/L) 
Baseline[1] 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
 
 
n 
 
 
n 
 
 
n 
 
Mean (SD) 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
Median 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
Min, Max 
x, x 
 
 
x, x 
 
 
x, x 
 
 
x, x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
n 
 
n 
n 
 
n 
n 
 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
x.x (x.xx) 
x.x (x.xx) 
 
Median 
x 
x 
 
x 
x 
 
x 
x 
 
x 
x 
 
Min, Max 
x, x 
x, x 
 
x, x 
x, x 
 
x, x 
x, x 
 
x, x 
x, x 
ALT (SGPT)  
(U/L) 
… 
 
Abbreviations: ALT (SGPT), alanine aminotransferase; AST (SGOT), aspartate aminotransferase; BUN, blood urea nitrogen; GGT, gamma glutamyl transferase 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug.  
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for regularly-collected chemistry parameters: Alkaline Phosphatase (U/L), Total Bilirubin (µmol/L), Direct Bilirubin (µmol/L), GGT (µmol/L), BUN (mmol/L), 
Creatinine (µmol/L), Sodium (mmol/L), Potassium (mmol/L), Chloride (mmol/L). 
 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.6.4 
Chemistry – Shift from Baseline to Worst Post-Baseline Value by Parameter 
Safety Population 
 
Parameter 
Worst Post-Baseline Assessment[2] 
Vehicle 
(N= ) 
Baseline Assessment[1] 
 
BBI-4000 5% 
(N= ) 
Baseline Assessment[1] 
 
BBI-4000 10% 
(N= ) 
Baseline Assessment[1] 
 
BBI-4000 15% 
(N= ) 
Baseline Assessment[1] 
Low 
Normal 
High 
 
Low 
Normal 
High 
 
Low 
Normal 
High 
 
Low 
Normal 
High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AST (SGOT) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Normal 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
High 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT (SGPT) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
Normal 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
High 
n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) 
n (x.x%) 
n (x.x%)  n (x.x%) n (x.x%) 
n (x.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alkaline Phosphatase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ALT (SGPT), alanine aminotransferase; AST (SGOT), aspartate aminotransferase; BUN, blood urea nitrogen; GGT, gamma glutamyl transferase 
 
Note: Percentages are based on the number of subjects with a non-missing baseline value and at least one non-missing post-baseline value. 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug.  
[2] The worst post-baseline assessment is defined as the value numerically farthest outside the normal range across all post-baseline visits through the end of the study. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: Continue for regularly-collected chemistry parameters: Total Bilirubin, Direct Bilirubin, GGT, Albumin, Total Protein, BUN, Creatinine, Sodium, Potassium, Chloride 
 
 
 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.7.1 
Vital Signs – Univariate Summary by Parameter and Visit 
Safety Population 
 
Vehicle 
(N= ) 
 
BBI-4000 5% 
(N=   ) 
 
BBI-4000 10% 
(N=   ) 
 
BBI-4000 15% 
(N=   ) 
Vital Sign 
Visit 
Observed 
Value 
Change from 
Baseline 
 
Observed 
Value 
Change from 
Baseline 
 
Observed 
Value 
Change from 
Baseline 
 
Observed 
Value 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
Systolic Blood Pressure (mmHg) 
Baseline[1] 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
 
 
n 
 
 
n 
 
 
n 
 
Mean (SD) 
x.x (x.xx) 
 
 x.x (x.xx) 
 
 x.x (x.xx) 
 
 
x.x (x.xx) 
 
 
Median 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
Min, Max 
x, x 
 
 
x, x 
 
 
x, x 
 
 
x, x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
n 
n 
n 
 
n 
n 
 
n 
n 
 
n 
n 
Mean (SD) 
x.x (x.xx) 
x.x (x.xx) 
 x.x (x.xx) 
x.x (x.xx) 
 x.x (x.xx) 
x.x (x.xx)  
x.x (x.xx) 
x.x (x.xx) 
 
Median 
x 
x 
 
x 
x 
 
x 
x 
 
x 
x 
 
Min, Max 
x, x 
x, x 
 
x, x 
x, x 
 
x, x 
x, x 
 
x, x 
x, x 
 
 
 
Day 15 
… 
Diastolic Blood Pressure (mmHg) 
… 
 
[1] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Notes: 
• 
Continue for remaining regularly-scheduled visits (Days 22, 29, 36, 43, and 57) 
• 
Continue for regularly-collected vital signs : Heart Rate (beats/minute), Respiratory Rate (breaths/minute), and Temperature (Co) 
 
 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Table 14.3.7.2 
Concomitant Medications 
Safety Population 
 
ATC Class / 
Generic Drug Name 
Vehicle 
(N= ) 
BBI-4000 5% 
(N= ) 
BBI-4000 10% 
(N= ) 
BBI-4000 15% 
(N= ) 
 
 
 
 
 
Subjects Receiving any Concomitant Medications 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
 
 
 
 
ATC Class #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
ATC Class #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #1 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
Generic Drug Name #2 
n (x.x%) 
n (x.x%) 
n (x.x%) 
n (x.x%) 
… 
 
 
 
 
 
 
 
 
 
Abbreviations: ATC, anatomic therapeutic chemical, WHO, World Health Organization 
 
Notes: 
• 
Concomitant medications are those medications received on or after the first dose of study drug. 
• 
Medications are coded to ATC drug class (level 4) and generic drug names using the WHO Drug dictionary enhanced, version B2 March 1, 2016. 
• 
At each level of summarization (any medication, ATC class, generic drug name), subjects reporting use of more than one medication are counted only once. 
 
Reference: Listing #(s) 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note:  
• 
Sort medications by descending order of ATC class incidence and by descending order of drug name incidence within ATC class, based on the overall incidence (ie, sum 
over all treatment groups). 
• 
When creating ATC level 4 drug class, utilize level 3 term if level 4 is missing in dataset and level 2 if both level 3 and level 4 are missing in the dataset 
• 
Repeat as Table 14.3.7.3 
Concomitant Therapies and Procedures, using (MedDRA), version 19.1 for SOC and PT. 
 
 
 
 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX C: LISTING LAYOUTS 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.1.7 
Randomization Scheme and Codes 
 
Subject ID 
Randomization Number 
Treatment Group Code 
Treatment Group 
Treatment Group Description 
 
 
 
 
xxx-xxxx 
xxxx 
A / 
B / 
C / 
                D 
Vehicle / 
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Vehicle gel / 
5% BBI-4000 in vehicle gel / 
10% BBI-4000 in vehicle gel / 
15% BBI-4000 in vehicle gel 
xxx-xxxx 
 
 
 
… 
 
 
 
 
 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
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                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.1 
Subject Disposition 
 
Subject ID 
Treatment 
Group 
Safety 
Population[1] 
mITT  
Population[2] 
PP  
Population[3] 
Date of First 
Dose 
Study Exit 
Date (Study 
Day[4]) 
Complete 
Treatment? 
Reason Subject Did 
Not Complete 
Treatment 
Complete 
Study? 
Primary Reason for Early 
Termination  
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
Yes / 
No 
Yes / 
No 
Yes / 
No 
ddMMMyyyy ddMMMyyyy 
(xx) 
Yes / 
No 
Adverse Event / 
Withdrawal by 
Subject / 
Physician Decision 
/ 
Protocol Violation / 
Lost to Follow-Up / 
Death / 
Pregnancy / 
Worsening 
Condition / 
Lack of Efficacy / 
Study Termination 
by Sponsor / 
Other 
Yes / 
No 
Normal Study Completion / 
Adverse Event / 
Withdrawal by Subject / 
Physician Decision / 
Protocol Violation / 
Lost to Follow-Up / 
Death / 
Pregnancy / 
Worsening Condition / 
Lack of Efficacy / 
Study Termination by Sponsor 
/ 
Other 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: mITT, Intent-to-Treat; PP, Per-Protocol 
 
[1] Safety population includes all subjects randomized in the study who received study drug at least once. Treatment group assignment is based on the treatment actually received. 
[2] mITT population includes all subjects who were randomized and dispensed study drug. Treatment group assignment is based on the planned treatment assigned. 
[3] PP population includes all Safety subjects who meet all inclusion/exclusion criteria, have not taken/applied prohibited concomitant medications, and have full data collected for all GSP visits.  
[4] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.2.1 
Protocol Violations/Deviations 
 
 
Subject ID Treatment Group 
Date of Deviation 
(Study Day[1]) 
Major Protocol 
Violation? 
Deviation/Violation Category Reason for Deviation/Violation 
Date of Sponsor 
Approval 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
ddMMMyyyy (xx) 
Yes / 
No 
Category 
Deviation 
ddMMMyyyy 
xxx-xxxx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.2.2 
Informed Consent and Eligibility Criteria 
 
 
Subject ID Treatment Group 
Subject Sign 
Informed 
Consent? 
Date Informed 
Consent Signed 
Time Informed  
Consent Signed 
Protocol 
Version 
Does subject meet  
all eligibility criteria? 
If No, 
Criterion Not 
Met 
Inclusion/Exclusion Criteria Waivers 
Was Waiver 
Granted? 
Date of  
Waiver 
Who Granted the 
Waiver? 
 
 
 
 
 
 
 
 
 
xx-xxx Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Yes / 
No 
ddMMMyyyy 
hh:mm 
Original 
November 22, 
2016 /  
Version 1 
22FEB2017 
Yes /  
No 
Inclusion # / 
Exclusion # 
Yes /  
No 
ddMMMyyyy Text 
 
 
 
 
 
 
Inclusion # / 
Exclusion # 
Yes / 
 No 
ddMMMyyyy Text 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
xx-xxx 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.3 
Subjects Excluded from the Efficacy Analysis 
 
Subject ID Treatment Group 
mITT Population[1] 
PP Population[2] Reason for Exclusion from the Efficacy Analysis 
 
 
 
 
 
xx-xxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Yes / 
No 
Yes / 
No 
Reason (e.g., screen failure, subject did not receive study drug, protocol violation, etc.), 
including any relevant specifications 
xx-xxx 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
Abbreviations: mITT, Intent-to-Treat; PP, Per-Protocol 
 
[1] mITT population includes all subjects who were randomized and dispensed study drug. Treatment group assignment is based on the planned treatment assigned. 
[2] PP population includes all Safety subjects who meet all inclusion/exclusion criteria, have not taken/applied prohibited concomitant medications, and have full data collected for all GSP visits. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 90 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.4.1 
Demographics 
 
Subject ID Treatment Group 
Date of Birth Age (years) Sex 
If Female, is subject of 
childbearing potential? 
Ethnicity 
Race 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
ddMMMyyyy 
xx 
Male / 
Female 
Yes / 
No 
Hispanic or Latino / 
Not Hispanic or Latino 
American Indian or Alaska Native / 
Asian / 
Black or African American / 
Native Hawaiian or Other Pacific Islander / 
White / 
Other 
xxx-xxxx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: If multiple races are reported for a given subject, display all that are reported in the “Race” column, separated by a semicolon.  
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 91 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.4.2 
Medical History 
 
Subject ID Treatment Group System Organ Class[1] 
Condition 
Onset Date 
Resolution Date 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Body System 
Condition / Diagnosis / Surgery 
ddMMMyyyy 
ddMMMyyyy / 
Ongoing 
 
 
Body System 
 
 
 
 
… 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
[1] Medical history events are coded to system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
 
Path\filename.sas ddmmmyyyy hh:mm 
  
Programming Note: Sort conditions based on onset date. If partial onset dates are reported (e.g., month and year only), separate out the portions of the date to sort separately by year, then 
month, then day.  
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 92 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.5.1 
Study Drug Dosing  
 
Subject ID 
Treatment 
Group 
Start of Study 
Drug 
Administration 
End of Study Drug 
Administration 
 (Study Day[1]) 
Any 
Application 
Deviations? 
Deviation Start 
Date (Study Day[1]) 
Deviation End 
Date (Study Day[1]) 
Deviation 
Type 
Axilla 
Reason for Deviation 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle / 
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
ddMMMyyyy 
 
ddMMMyyyy 
(xx) 
Yes / 
No / 
Unknown 
ddMMMyyyy 
(xx) 
ddMMMyyyy 
(xx) 
Missed / 
Other 
(specify) 
Right / 
Left / 
Both 
Adverse Event / 
Other (specify) 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 93 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Listing 16.2.5.2 
Study Drug Administration and Accountability 
 
Subject ID 
Treatment 
Group 
Pump 
 Container 
Pump 
Dispensed? 
If No, 
Specify 
Date 
Dispensed 
(Study Day[1]) 
Kit # 
Dispensed 
Weight (g) 
Pump 
Returned? 
If No, 
Specify 
Date Returned 
(Study Day[1]) 
Returned 
Weight (g) 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
1 
Yes /  
No 
text 
ddMMMyyyy 
(xx) 
xxxx 
xx.x 
Yes / 
No 
text 
ddMMMyyyy 
(xx) 
xx.x 
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 94 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.5.3 
Study Drug Exposure and Compliance 
 
Subject ID 
Treatment Group 
Expected 
Number of Doses 
Actual Number 
of Doses 
Study Drug 
Compliance (%)[1] 
Duration of Exposure 
(Days)[2] 
Total Drug 
Delivered (g)[3] 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle / 
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
xx 
xx 
xx.x 
ddMMMyyyy 
(xx) 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study drug compliance is calculated as the number of doses received / the expected number of doses x 100 
[2]Duration of exposure to study treatment is calculated as the date of last dose of study drug – the date of first dose of study drug + 1. 
[3] Total drug delivered is calculated as total grams dispensed – total grams returned. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 95 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.1 
Hyperhidrosis Disease Severity Measure-Axilla 
Part 1 of 2 
 
Question Number 
Question Text 
Responses 
1a 
Since you woke up yesterday, how often did you experience damp or wet clothing because of your 
underarm sweating while you were awake? 
 0-None of the time 
 1-Almost none of the time, 
 2-Some of the time, 
 3-Most of the time 
 4-All of the time 
 
 
 
1b 
Since you woke up yesterday, how often did you experience underarm sweating for no apparent reason 
while you were awake? 
 0-None of the time 
 1-Almost none of the time, 
 2-Some of the time, 
 3-Most of the time 
 4-All of the time 
 
 
 
2a 
Since you woke up yesterday, how severe was your experience with underarm sweating when you felt 
nervous, stressed or anxious? 
 0-I did not experience this 
 1-Mild 
 2-Moderate  
 3-Severe  
 4-Very severe  
 
 
 
2b 
Since you woke up yesterday, how severe was your experience with damp or wet clothing because of 
your underarm sweating? 
0-I did not experience this 
 1-Mild 
 2-Moderate  
 3-Severe  
 4-Very severe 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
Programming Note: Listing continues on next page 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 96 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 Listing 16.2.6.1 
 Hyperhidrosis Disease Severity Measure-Axilla 
 Part 1 of 2 
 
Question Number 
Question Text 
Responses 
 
 
 
2c 
Since you woke up yesterday, how severe was your experience with underarm sweating after almost none or no 
physical exercise?  
0-I did not experience this 
 1-Mild 
 2-Moderate  
 3-Severe  
 4-Very severe 
 
 
 
2d 
Since you woke up yesterday, how severe was your experience with underarm wetness? 
0-I did not experience this 
1-Mild 
2-Moderate 
3-Severe 
4-Very severe 
 
 
 
2e 
Since you woke up yesterday, how severe was your experience with underarm sweating for no apparent reason? 
0-I did not experience this 
1-Mild 
2-Moderate 
3-Severe 
4-Very severe 
 
 
 
2f 
Since you woke up yesterday, how severe was your experience with underarm sweating that was unmanageable? 
 0-I did not experience this 
 1-Mild 
 2-Moderate  
 3-Severe  
 4-Very severe 
 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Listing continues on next page. 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 97 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.1 
Hyperhidrosis Disease Severity Measure-Axilla 
Part 1 of 2 
 
Question Number 
Question Text 
Responses 
 
 
 
2g 
Since you woke up yesterday, how severe was your experience with underarm sweating 
when you were cool? 
 0-I did not experience this 
 1-Mild 
 2-Moderate  
 3-Severe  
 4-Very severe 
 
 
 
3a 
Since you woke up yesterday, describe your feeling the need to change clothes because 
of underarm sweating? 
 0-Not at all 
 1-Slight, 
 2-Moderate 
 3-Strong 
 4-Very strong 
 
 
 
3b 
Since you woke up yesterday, describe your feeling the need to wipe sweat from your 
underarms? 
 0-Not at all 
 1-Slight, 
 2-Moderate 
 3-Strong 
 4-Very strong 
 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Listing continues on next page. 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
Page x of y
 
Confidential 
 
Page 98 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.1 
Hyperhidrosis Disease Severity Measure-Axilla 
Part 1 of 2 
 
Question Number 
Question Text 
Responses 
 
 
 
4 
Since you woke up yesterday, how much of the time did you experience excessive 
underarm sweating while you were awake? 
 0-None of the time 
 1-Almost none 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? 
0-I did not have underarm sweating (completely dry) 
1-I had underarm sweating but it was mild (moist) 
2-I had underarm sweating and it was moderate (damp) 
3-I had underarm sweating and it was severe (wet) 
4-I had underarm sweating and it was very severe (soaking) 
 
 
 
6 
How normal was your level of physical exercise and stress since you woke up yesterday? 
choose 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. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
Page x of y
 
Confidential 
 
Page 99 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Listing 16.2.6.1 
Hyperhidrosis Disease Severity Measure-Axilla 
Part 2 of 2 
 
Subject 
ID 
Treatment  
Group 
Visit 
HDSM-Ax  
Completed? 
Assessment  
Date 
(Study Day[1]) 
HDSM-Ax Scoring Questions 
 
 
 
1a 
1b 
2a 
2b 
2c 
2d 
2e 
2f 
2g 
3a 
3b 
Mean[2] 
4 
5 
6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
Visit 1 
(Screening) 
Yes / 
No 
ddMMMyyyy 
(xx) 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
0-4 
text 
 
 
Visit 4 
(Rescreening) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: HDSM-Ax, Hyperhidrosis Disease Severity Measure-Axilla  
 
Note: Questions Q1a-Q5 specify one response per question; Q6 may respond with all that apply. 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Mean is calculated as the total score for questions 1 through 3 (11 sub-items) divided by the number of questions answered. Subjects must answer at least 6 of 11 sub-items to be 
evaluable. 
[3] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Continue for Baseline [3], Days 8, 15, 22, 29, 36, 41, 42, 43, 57 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 100 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.2 
Gravimetric Sweat Production Measurements 
 
 
 
 
 
 
Right Axilla 
 
Left Axilla 
 
 
Subject 
ID 
Treatment  
Group 
Visit 
Gravimetric  
Assessment Performed? 
Assessment Date 
(Study Day[1]) 
 
Pre-test 
Weight 
Start 
Time 
End Time 
Post-test 
Weight 
 
 
Pre-test 
Weight 
Start 
Time 
End Time 
Post-test 
Weight 
Total 
Sweat 
Weight[2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 5% 
/ 
BBI-4000 
10% / 
BBI-4000 
15% 
Visit 1 (Screening) 
Yes / 
No 
 
xx.x 
hh:mm 
hh:mm 
xx.x 
 
xx.x 
hh:mm 
hh:mm 
xx.x 
xx.x 
 
 
Visit 2 (GSP1) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: GSP, gravimetrically measured sweat production 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Total sweat weight is the sum of the post-test weights from the right axilla and left axilla. 
[3] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Continue for Visits 3 and 4, Baseline[3], and Days 8, 15, 22, 29, 36, 41, 42, 43, 57 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 101 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
 
 
 
Listing 16.2.6.3 
Hyperhidrosis Disease Severity Scale 
 
Subject ID 
Treatment Group 
Visit 
Date of Assessment 
(Study Day[1]) 
                How would you rate the severity of your axillary hyperhidrosis? 
 
 
 
 
 
xxx-xxxx 
Vehicle / 
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
 
 
 
Visit 1 
(Screening) 
 
 
 
ddMMMyyyy 
(xx) 
 
 
 
(1) My sweating is never noticeable and never interferes with my daily activities / 
(2) My sweating is tolerable but sometimes interferes with my daily activities / 
(3) My sweating is barely tolerable and frequently interferes with my daily 
activities / 
(4) My sweating is intolerable and always interferes with my daily activities 
     
 
Visit 4 
(Rescreening) 
 
 
 
 
… 
 
 
 
 
 
 
 
xxx-xxxx 
… 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Continue for Visits 3 and 4, Baseline[2], and Days 8, 15, 22, 29, 36, 41, 42, 43, 57 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 102 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.4 
Dermatology Life Quality Index- Axilla 
Part 1 of 2 
 
Question Number 
Question Text 
Responses 
 
 
 
1 
Over the last week, how itchy, sore, painful or stinging has your underarm skin been? 
Very much 
 
 
A lot  
Almost none 
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  
Almost none 
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  
Almost none 
Not at all 
 
 
 
4 
Over the last week, how much has your underarm sweating influenced the clothes you wear? 
Very much 
A lot  
Almost none 
Not at all 
Not relevant 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming note: Listing continues on next page. 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 103 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.4 
Dermatology Life Quality Index- Axilla 
Part 1 of 2 
Question Number 
Question Text 
Responses 
 
 
 
5 
 
 
 
Over the last affected any social or leisure week, how much has your underarm sweating activities? 
 
 
 
 
Very much 
A lot  
Almost none 
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  
Almost none 
Not at all 
Not relevant 
 
 
 
7 
Over the last week, has your underarm sweating prevented you from working or studying? 
Very much 
A lot  
Almost none 
Not at all 
Not relevant 
 
 
 
 
If "No", over the last week how much has your underarm sweating been a problem at work or studying? 
A lot  
Almost none 
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  
Almost none 
Not at all 
Not relevant 
 
 
 
Path\filename.sas ddmmmyyyy hh:mm 
Programming note: Listing continues on next page. 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 104 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.6.4 
Dermatology Life Quality Index- Axilla 
Part 1 of 2 
Question Number 
Question Text 
Responses 
 
 
 
9 
 
 
 
Over the last week, how much has your underarm sweating caused any sexual difficulties? 
 
 
 
 
Very much 
A lot  
Almost none 
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  
Almost none 
Not at all 
Not relevant 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 105 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Listing 16.2.6.4 
Dermatology Life Quality Index 
Part 2 of 2 
 
Subject ID 
Treatment 
Group 
Visit 
DLQI 
Completed? 
Assessment 
Date (Study Day[1]) 
Question Number 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Total 
Score 
xxx-xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
Visit 4 (Rescreening) 
Yes / 
No 
ddMMMyyyy 
(xx) 
0-3 
0-3 
0-3 
0-3 
0-3 
0-3 
0-3 
0-3 
0-3 
0-3 
0-30 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: DLQI, Dermatology Life Quality Index-Axilla 
 
Note:  DLQI Total Score is calculated by summing the replies to Questions 1 through 10. 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 106 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.7.1 
Adverse Events 
 
 
Subject 
ID 
Treatment 
Group 
System Organ Class[1] / 
Preferred Term[1] / 
Event Name 
In the 
Treatment 
Area? 
 
Start Date  
(Study Day[2]) 
 
End Date 
(Study Day[2]) Serious Severity 
Relationship to  
Study Drug 
Action Taken with  
Study Treatment 
Action Taken to  
Treat Event 
Outcome 
 
 
 
 
 
 
 
 
 
 
 
xxx-
xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
System Organ Class / 
Preferred Term / 
Event Name 
Yes / 
No 
ddMMMyyyy 
(xx) 
ddMMMyyyy 
(xx) / 
Ongoing 
Yes / 
No 
Mild / 
Moderate / 
Severe 
Not Related / 
Unlikely Related / 
Possibly Related / 
Related 
None / 
Drug Interrupted / 
Drug Reduced / 
Drug Interrupted / 
Drug Withdrawn / 
Not Applicable / 
Unknown / 
Display all that are 
reported, separated 
by a comma 
None / 
Medication / 
Procedure or Therapy / 
Hospitalization /  
Discontinued from 
Study / 
Other / 
Unknown  
Display all that are 
reported, separated by a 
comma 
Fatal / 
Not Recovered/Not 
Resolved/ 
Recovered/Resolved
/ 
Recovered/Resolved 
with Sequelae / 
Recovering/Resolvin
g/ 
Unknown 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-
xxxx 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Adverse events are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
[2] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 107 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.7.2 
Local Tolerability Assessments – Subject Assessments 
 
Subject ID 
Visit 
Assessment Performed? 
Visit Date 
 (Study Day[1]) 
Right Axilla 
 
Left Axilla 
Treatment Group 
Itching 
Burning 
 
Itching 
Burning 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle / 
BBI-4000 5% / 
BBI-4000 10% / 
BBI-400 15% 
Baseline [2] 
Yes  / 
No 
ddMMMyyyy 
 (xx) 
0-4 
 
0-4 
 
 
0-4  
0-4  
 
Day 8 
 
 
 
 
 
 
 
 
Day 15 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
Day 36 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
Day 57 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  Subjects self-evaluate Itching and Burning for each axilla prior to the Investigator’s evaluation. 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 108 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.7.3 
Local Tolerability Assessments – Investigator Assessments 
 
Subject 
ID 
Visit 
Assessment Performed? 
Visit Date 
 (Study Day[1]) 
Right Axilla 
 
Left Axilla 
Treatment Group 
Dryness 
Scaling 
Erythema  
Dryness 
Scaling 
Erythema 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle / 
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Baseline [2] 
Yes  / 
No 
ddMMMyyyy 
 (xx) 
0-4  
 
0-4  
 
0-4  
 
 
0-4  
 
0-4  
 
0-4  
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
Day 15 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
Day 36 
 
 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
Day 57 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  Investigator evaluates Dryness, Scaling, and Erythema for each axilla after subject’s evaluation. 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
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Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.1 
Hematology 
Part 1 of 3 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
RBC Count 
(1012/L) 
Hematocrit 
(L/L) 
Hemoglobin 
(g/L) 
MCH 
(pg) 
MCHC 
(g/L) 
MCV 
(fL) 
Platelet Count 
(109/L) 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 
5%/ 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy (xx) HH:MM 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: CS, clinically significant; H, high; L, low; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red 
blood cell 
 
Note: H = high; L = low is displayed if result is outside the reference range. 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
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Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.1 
Hematology 
Part 2 of 3 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
WBC Count 
(109/L) 
Reticulocyte 
Count (109/L) 
Neutrophils 
(%) 
Lymphocytes 
(%) 
Monocytes 
(%) 
Eosinophils 
(%) 
Basophils  
(%) 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy 
(xx) 
HH:MM x.x CS, H/L x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L x.x CS, H/L 
x.x CS, H/L 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: CS, clinically significant; H, high; L, low; WBC, white blood cell  
 
Note: H = high; L = low is displayed if result is outside the reference range. 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
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Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.1 
Hematology 
Part 3 of 3 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
Test 
 
Unit 
 
Result 
 
Alert 
Clinically Significant 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% 
/ 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy (xx) HH:MM Test Name #1 
Unit 
xxx 
High / 
Low 
Yes / 
null 
 
 
Day 43 
 
 
Test Name #2 
 
 
 
 
 
 
 
 
Test Name #3 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Only those tests that are collected as part of the hematology panel but not presented in Parts 1 and 2 should appear in this part. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.2 
Chemistry 
Part 1 of 3 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) Collection Time 
AST (SGOT) 
(U/L) 
ALT (SGPT) 
(U/L) 
Alkaline Phosphatase 
(U/L) 
Total Bilirubin 
(µmol/L) 
Direct Bilirubin 
(µmol/L) 
Albumin 
(g/L) 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Screening 
ddMMMyyyy 
(xx) 
HH:MM 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
 
 
Day 43 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AST (SGOT), aspartate aminotransferase; ALT (SGPT), alanine aminotransferase; BUN, blood urea nitrogen; CS, clinically significant; H, high; L, low 
 
Note: H = high; L = low is displayed if result is outside the reference range. 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
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Page 113 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.2 
Serum Chemistry 
Part 2 of 3 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
Total Protein 
(g/L) 
BUN  
(mmol/L) 
Creatinine 
(µmol/L) 
Sodium 
(mmol/L) 
Potassium 
(mmol/L) 
Chloride (mmol/L) 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Screening 
ddMMMyyyy (xx) HH:MM 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
x.x CS, H/L 
 
 
Day 43 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: CO2, Carbon Dioxide; CS, clinically significant; H, high; L, low 
 
Note: H = high; L = low is displayed if result is outside the reference range. 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 114 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.2 
Serum Chemistry 
Part 3 of 3 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
Test 
 
Unit 
 
Result 
 
Alert 
Clinically Significant 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% 
/ 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy (xx) HH:MM Test Name #1 
Unit 
xxx 
High / 
Low 
Yes / 
null 
 
 
Day 43 
 
 
Test Name #2 
 
 
 
 
 
 
 
 
Test Name #3 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Only those tests that are collected as part of the chemistry panel but not presented in Parts 1 and 2 should appear in this part. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.3 
Urinalysis 
Part 1 of 2 
 
   Subject 
ID 
Treatment 
Group 
 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
 
Appearance 
Bilirubin 
(mg/dL) 
 
Color 
Glucose 
(mg/dL) 
 
Ketones 
 
Nitrite 
 
pH 
Protein 
Occult 
Blood 
Specific Gravity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy 
(xx) 
HH:MM 
Result 
Result 
Result 
Result 
Result 
Result x.x CS, 
H/L 
Result 
Result 
x.x CS, H/L 
 
 
Day 43 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: CS, clinically significant; H, high; L, low 
 
Note: H = high; L = low is displayed if result is outside the reference range. 
 
 [1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
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Page 116 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
 
Listing 16.2.8.3 
Urinalysis 
Part 2 of 2 
 
Subject 
ID 
Treatment 
Group 
Visit 
Collection Date 
(Study Day[1]) 
Collection 
Time 
Test 
 
Unit 
 
Result 
 
Alert 
Clinically Significant 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% 
/ 
BBI-4000 
10% / 
BBI-4000 
15% 
Screening 
ddMMMyyyy (xx) HH:MM Test Name #1 
Unit 
xxx 
High / 
Low 
Yes / 
null 
 
 
Day 43 
 
 
Test Name #2 
 
 
 
 
 
 
 
 
Test Name #3 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 [1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Only those tests that are collected as part of the urinalysis panel but not presented in Part 1 should appear in this part. 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 117 of 122 
 


Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.8.4 
Urine Pregnancy Test 
 
Subject ID 
Treatment Group 
Visit 
Was a Pregnancy Test performed? 
Collection Date (Study Day[1]) 
Result 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Screening 
Yes / 
No 
ddMMMyyyy (xx) 
Positive / 
Negative / 
N/A 
 
 
Baseline[2] 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
Abbreviations: N/A, not applicable 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Continue for Days 29 and 43 
 
 
 
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Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.9.1 
Vital Signs 
 
 
Subject ID 
Treatment 
Group 
Visit 
Visit Date 
 (Study Day[1]) 
Height[2] 
(cm) 
Weight[2] 
(kg) 
BMI[3] 
(kg/m2) 
Blood 
Pressure 
(mmHg) 
Heart Rate  
(bpm) 
Respiratory 
Rate 
(breaths/min) 
Temperature 
(°C) 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% 
/ 
BBI-4000 15% 
Visit 4 
(Rescreening) 
ddMMMyyyy 
(xx) 
xx.x 
xx.x 
xx.x 
xxx – xxx 
xxx 
xxx 
xx.x 
 
 
Baseline[4] 
 
 
 
 
xxx – xxx 
xxx 
xxx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: BMI, body mass index 
 
[1] Time (days) relative to date of first dose of study drug 
[2] Height, weight, and BMI are collected at the Visit 4 only. 
[3] BMI is calculated as weight (kg) / [height (cm) / 100]2. 
[4] Baseline is defined as the last available measurement taken prior to the first dose of study drug. 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note: Continue for Days 8, 15, 22, 29, 36, 43, and 57 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.9.2 
Physical Examination 
 
Subject ID 
Treatment Group 
Visit 
Was a Physical Examination performed? 
Assessment Date 
 (Study Day[1]) 
Were there any abnormal findings on the physical 
examination? 
 
 
 
 
xxx-xxxx 
Vehicle /  
BBI-4000 5% / 
BBI-4000 10% / 
BBI-4000 15% 
Visit 4 (Rescreening) 
Yes / 
No 
ddMMMyyyy (xx) / 
Not Done 
Yes /  
No 
 
 
 
 
 
Unscheduled Visit 
… 
 
 
 
… 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
… 
 
 
 
 
 
 
 
 
[1] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.9.3 
Prior and Concomitant Medications 
 
Subject  
ID 
Treatment 
Group 
Any Medications  
to Report? 
ATC Class[1] / 
Generic Drug Name[1] / 
Medication Name 
In the 
Treatment 
Area? 
 
 
Phase[2] 
Start Date 
(Study Day[3]) 
End Date 
(Study Day[3]) Dose 
Unit 
Route 
Frequency 
Indication 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 
5% / 
BBI-4000 
10% / 
BBI-4000 
15% 
Yes / 
No 
ATC Class / 
Generic Drug Name / 
Medication Name 
Yes / 
No 
P / 
C / 
P, C 
ddMMMyyyy 
(xx) 
ddMMMyyyy 
(xx) / 
Ongoing 
Dose 
Unit 
Route 
Frequency 
Medical History: 
specify /  
Adverse Event: 
specify /  
Hyperhidrosis / 
Other: Specify 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ATC, anatomic therapeutic chemical; WHO, World Health Organization  
 
Note: Concomitant medications are those medications received after the first dose of study drug. 
 
[1] Medications are coded to ATC class (level 4) and drug names using the WHO Drug dictionary enhanced, version B2 March 1, 2016. 
[2] The study phase during which each medication was received. P = prior (i.e., received prior to the first dose of study drug); C = concomitant (i.e., received on or after the first dose of study 
drug); P, C = both prior and concomitant 
[3] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
Programming Note:  
• 
If specifications for indications are reported as an AE or MH #, merge with AE/MH data to present the actual reported event as the specification. 
• 
When creating ATC level 4 drug class, utilize level 3 term if level 4 is missing in dataset and level 2 if both level 3 and level 4 are missing in the dataset 
 
 
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Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
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Brickell Biotech, Inc. 
                                                                                            Statistical Analysis Plan 
BBI-4000-CL-203 
 Version 2.0; 27 July 2017 
 
Listing 16.2.9.4 
Prior and Concomitant Therapy and Procedures 
 
Subject  
ID 
Treatment 
Group 
Any Concomitant 
Therapies/Procedures? 
System Organ Class[1] / 
Preferred Term[1]/ 
Therapy/Procedure Name 
 
Phase[2] 
Start Date 
(Study Day[3]) 
End Date 
(Study Day[3]) 
In the 
Treatment Area? 
If Yes, 
Specify Axilla Frequency Indication 
 
 
 
 
 
 
 
 
 
xxx-xxxx Vehicle /  
BBI-4000 5% / 
BBI-4000 10% 
/ 
BBI-4000 15% 
Yes / 
No 
Body System / 
Preferred Term / 
Therapy/Procedure Name 
P / 
C / 
P, C 
ddMMMyyyy 
(xx) 
ddMMMyyyy 
(xx) / 
Ongoing 
Yes / 
No 
Right/ 
Left/ 
Both 
Frequency Medical History: 
specify /  
Adverse Event: 
specify /  
Hyperhidrosis / 
Other: Specify 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Concomitant therapies/procedures are those therapies/procedures received after the first dose of study drug. 
 
[1] Therapies/Procedures are coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA), version 19.1. 
[2] The study phase during which each medication was received. P = prior (i.e., received prior to the first dose of study drug); C = concomitant (i.e., received on or after the first dose of study drug); P, 
C = both prior and concomitant 
[3] Time (days) relative to date of first dose of study drug 
 
Path\filename.sas ddmmmyyyy hh:mm 
 
 
 
 
 
 
 
 
 
 
 
Brickell Biotech, Inc. 
Database Date/Analysis: DDMMMYYYY/Draft
BBI-4000-CL-203 
 
Page x of y
 
Confidential 
 
Page 122 of 122