Clinical trial NCT03785587
Conditions: Primary Axillary Hyperhidrosis
Sponsor: Botanix Pharmaceuticals
Start date: 2018-12-21; Completion date: 2019-09-06
Enrollment: 21 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Hyperhidrosis is a disorder of abnormal excessive sweating. Primary hyperhidrosis (armpits, hands, and feet) affects approximately 4.8% of the US population and is believed to be caused by an overactive cholinergic response of the sweat glands. Sofpironium bromide (BBI-4000) is a novel soft-drug in development for the topical treatment of hyperhidrosis. This Phase 2 study will assess the long-term safety, tolerability, pharmacokinetics and efficacy of sofpironium bromide gel applied topically to pediatric subjects with axillary hyperhidrosis.

Detailed description:
This is an open-label, phase 2 long-term study designed to evaluate the safety, local tolerability, pharmacokinetics and efficacy of sofpironium bromide gel when applied topically to the axillae.

Subjects will apply the gel once daily at bedtime, to both axillae.

A maximum of 24 subjects, will be enrolled to receive sofpironium bromide gel, 15%.

Adverse events, vital signs, and local tolerability assessments will be collected at each visit. Urine pregnancy tests will be taken throughout the course of the study for women of child bearing potential. Blood and urine samples will be collected and analyzed for pharmacokinetics, routine hematology, chemistry, and urinalysis parameters at specified visits. Patient-reported outcome assessments will be recorded during the study at predefined time points.

The study will be comprised of a total of 8 scheduled visits to take place over a 26 week period.

Arms: arm 1: Sofpironium Bromide Gel, 15%, applied once daily to each axilla for 24 weeks
Interventions: intervention 1: Sofpironium Bromide Gel, 15%
Intervention descriptions: intervention 1: Sofpironium Bromide Gel, 15%

Protocol documents:
Prot_000.pdf: 
Confidential Statement 
This document contains confidential information of Brickell Biotech Inc. 
Do not copy or distribute without written permission of the Sponsor. 
A Multi-Center, Open-Label Extension Study to Assess the Long-Term Safety, 
Tolerability and Pharmacokinetics of Sofpironium Bromide Gel, 15% Applied 
Topically to Children and Adolescents, ≥9 to ≤17 Years of Age, Previously Enrolled in 
Study BBI-4000-CL-105 
Compound: 
Sofpironium Bromide Gel, 15% 
US IND Number: 
121256 
Clinical Protocol Number: 
BBI-4000-CL-108 
Phase of Development: 
2 
 Sponsor: 
Brickell Biotech Inc. 
5777 Central Ave., Suite 102 
Boulder, CO 80301 
Medical Monitor: 
Brandon Kirsch, MD 
Brickell Biotech, Inc. 
5777 Central Ave., Suite 102 
Boulder, CO 80301 
Phone: 720-619-4966 
Serious Adverse Event Reporting: 
Fax: +1 (866) 666-7392  
Email: safety@brickellbio.com 
Protocol Version: 
Original  
21 September 2018 
Previous Protocol Versions: 
Version 
Version Date 
GCP Statement 
This study will be conducted in accordance with the Food and Drug Administration (FDA) 
and International Council on Harmonisation (ICH) guidelines on current Good Clinical 
Practice (GCP), Good Laboratory Practice (GLP) guidelines, and the principles of the 
Declaration of Helsinki. 
NCT03785587




Brickell Biotech, Inc. 
21 September 2018 
Protocol BBI-4000-CL-108 
Page 3 of 60 
 
Confidential 
 
 
AGREEMENT OF INVESTIGATOR COMPLIANCE 
I have read the protocol entitled “A Multi-Center, Open-Label Extension Study to Assess the Long-
Term Safety, Tolerability and Pharmacokinetics of Sofpironium Bromide Gel, 15% Applied 
Topically to Children and Adolescents, ≥9 to ≤17 Years of Age, Previously Enrolled in Study BBI-
4000-CL-105” and:  
• 
Agree that the protocol contains all the information necessary to conduct the study;  
• 
Agree to conduct the study in accordance with the protocol and as subsequently amended by the 
Sponsor (or designee), except when to protect the safety, rights or welfare of study subjects;  
• 
Agree to conduct the study in accordance with applicable federal, state and local laws and 
regulations, and in accordance with the Food and Drug Administration (FDA) and International 
Council on Harmonisation (ICH) guidelines on current Good Clinical Practice (GCP), and the 
principles of the Declaration of Helsinki; and  
• 
Agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
 
 
 
 
 
 
 
 
Investigator: Print Name 
 
 
 
 
Site ID Number 
Signature 
 
Date 


Brickell Biotech, Inc. 
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Protocol BBI-4000-CL-108 
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Confidential 
 
 
ABBREVIATIONS 
Abbreviations 
Definitions 
AE 
Adverse event 
BP 
Blood pressure 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Act 
Cmax 
Maximum concentration 
CRO 
Contract Research Organization 
Ctrough 
Trough concentration 
CV 
Coefficient of Variation 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EOT 
End of Treatment 
ET 
Early Termination 
EU 
European Union 
FDA 
Food and Drug Administration 
g 
Grams 
GCP 
Good Clinical Practice 
HDSM-Ax 
Hyperhidrosis Disease Severity Measure-Axillary 
HDSM-Ax, Child 
Hyperhidrosis Disease Severity Measure-Axillary, Child 
HIPAA 
Health Insurance Portability and Accountability Act 
hr, h, hrs 
Hour(s) 
HR 
Heart rate 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IUD 
Intrauterine device 


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Abbreviations 
Definitions 
kg 
Kilogram(s) 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram(s) 
min 
Minute(s) 
mL 
Milliliter(s) 
mm 
Millimeter(s) 
mmHg 
Millimeter of mercury 
NF 
National Formulary 
ng 
Nanogram 
nM 
Nanomolar 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PK 
Pharmacokinetics 
QD 
Once daily 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SRC 
Study Review Committee 
SSRI 
Selective serotonin re-uptake inhibitors 
TBV 
Total blood volume 
TEAE 
Treatment-emergent adverse event 
tmax 
Time to maximum concentration 
UPT 
Urine pregnancy testing 
US 
United States of America 
USP 
United States Pharmacopeia 
WHODD 
World Health Organization Drug Dictionary 


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Protocol BBI-4000-CL-108 
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PROTOCOL SYNOPSIS 
Study Title 
A Multi-Center, Open-Label Extension Study to Assess the Long-Term Safety, 
Tolerability and Pharmacokinetics of Sofpironium Bromide Gel, 15% Applied 
Topically to Children and Adolescents, ≥9 to ≤17 Years of Age, Previously Enrolled in 
Study BBI-4000-CL-105 
Study Number 
BBI-4000-CL-108 
Study Objectives 
Primary Objectives: 
Safety 
To assess the long-term safety and tolerability of sofpironium bromide gel, 15% 
applied topically once daily for up to 24 weeks in children and adolescent subjects, >9 
to ≤17 years of age, with axillary hyperhidrosis.  
Pharmacokinetic 
To assess the systemic exposure (Ctrough) of sofpironium and its primary metabolite 
(BBI-4010), following topical application of ~0.67 mL of sofpironium bromide gel, 
15% applied topically to each axilla, once daily (QD) for up to 24 weeks. 
Exploratory Objectives: 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) and 
Hyperhidrosis Disease Severity Measure-Axillary, Child (HDSM-Ax, Child) 
in pediatric subjects, ≥9 to ≤17 years of age, with axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Summary 
Questions; duration (No. 4) and severity (No. 5) in pediatric subjects, ≥9 to 
≤17 years of age, with axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Patient Global Impression of Severity (PGI-S) in pediatric subjects, ≥9 to ≤17 
years of age, with axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Patient Global Impression of Change (PGI-C) in pediatric subjects, ≥9 to ≤17 
years of age, with axillary hyperhidrosis 
 
Study Endpoints 
Primary Endpoints: 
Safety 
• 
Incidence and severity of application site burning, itching, stinging, scaling 
and erythema 
• 
Incidence and severity of all adverse events (AEs) and their relationship to 
study drug 
• 
Incidence of clinically meaningful change from baseline in safety laboratory 
parameters, physical examinations, 12-lead electrocardiograms (ECGs) and 
vital signs 
• 
Proportion of subjects who discontinue treatment due to an AE 
Pharmacokinetics 


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Protocol BBI-4000-CL-108 
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Determination of plasma concentrations (Ctrough) of sofpironium, and BBI-4010, at 
Week 4 and Week 24 (end of treatment) following 24 weeks of QD topical application 
of sofpironium bromide gel, 15%. 
Exploratory Endpoints 
• 
Change of HDSM-Ax (≥12 years of age) or HDSM-Ax, Child (≥9 to <12 
years of age) from baseline to end of treatment. 
• 
Change of HDSM-Ax Summary Questions; duration (No. 4) and severity (No. 
5) from baseline to end of treatment. 
• 
Change of PGI-S from baseline to end of treatment. 
• 
PGI-C at Week 12 (Day 84) and end of treatment. 
Study Assessments 
Safety 
• 
Adverse events at all visits 
• 
Local application site tolerability assessments (including burning, itching, 
stinging, scaling and erythema) at all visits through and including Week 24 
[Day 168], and Week 26 (Day 182), if applicable 
• 
Vital signs (heart rate [HR], blood pressure (BP), respiratory rate and 
temperature) at all visits through and including Week 26 
• 
12-lead ECG at Week 0 (Day 1), Week 4 (Day 28), Week 24 (Day 168), and 
Week 26 (Day 182), if applicable 
• 
Laboratory testing (hematology, chemistry and urinalysis) at Week 0 (Day 1), 
Week 4 (Day 28), Week 24 (Day 168), and Week 26 (Day 182), if applicable 
• 
Pregnancy test (females) at all visits through and including Week 26 (Day 
182) 
• 
Abbreviated physical examination at all visits through and including Week 26 
(Day 182) 
Pharmacokinetics 
• 
Plasma samples will be collected ≥12 hours after last dose on Week 0 (Day 1) 
[per Day 8/Visit 4 of Study BBI-4000-CL-105], Week 4 (Day 28), and Week 
24 (Day 168). 
Efficacy 
• 
HDSM-Ax or HDSM-Ax, Child as assessed by the subject at all visits through 
and including Week 24 (Day 168) 
• 
HDSM-Ax or HDSM-Ax, Child Summary Questions; duration (No. 4) and 
severity (No. 5) as assessed by the subject at all visits through and including 
Week 24 (Day 168) 
• 
Change in PGI-S as measured by the subject at all visits through and including 
Week 24 (Day 168) 
• 
PGI-C as measured by the subject at Week 12 (Day 112) and Week 24 (Day 
168) 
Study Population 
Subjects enrolled in this study will be males and females, ≥9 years to ≤17 years of age, 
with axillary hyperhidrosis who participated in and completed Study BBI-4000-CL-
105. 
Study Methodology 
This multi-center, open-label extension study will evaluate the long-term safety, 
tolerability and pharmacokinetics of topical sofpironium bromide gel, 15%, when 


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Protocol BBI-4000-CL-108 
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Confidential 
 
 
applied QD for up to 6 months in pediatric subjects ≥9 years to ≤17 years of age with 
axillary hyperhidrosis previously enrolled in Study BBI-4000-CL-105.  
Following completion of the initial PK and safety study (Study BBI-4000-CL-105), 
subjects will be provided the opportunity to enter this 6-month open-label extension 
study. Subjects will be screened for eligibility at Day 8 of Study BBI-4000-CL-105 
(last PK sample collection under BBI-4000-CL-105 study). Therefore, for participating 
subjects, the final treatment visit (i.e., Day 8/Visit 4) of Study BBI-4000-CL-105 and 
the Screening/Enrollment visit (i.e., Week 0 [Day 1]) of Study BBI-4000-CL-108 
(long-term extension study) will take place simultaneously. 
Subjects (parent/guardian) will be dispensed one container of sofpironium bromide gel, 
15% each month at Visits 1-6. Subjects (and parent/guardian) will be instructed on the 
correct application procedure for sofpironium bromide gel, 15% (to be applied QD 
before bedtime to both axilla for up to 24 weeks). 
Vital signs, review of concomitant medications, assessment of AEs, completion of 
patient-reported outcomes (HDSM-Ax or HDSM-Ax, Child, and PGI-S), and urine 
pregnancy tests (UPT) for all females will be done each visit. Application site 
tolerability will be assessed at all visits through the end of treatment (EOT) at Week 24 
(Day 168). Blood and urine for safety testing will be collected and analyzed at Week 4 
(Day 28) and Week 24 (Day 168) for routine hematology, chemistry, and urinalysis 
parameters. ECGs will be assessed at Week 0 (pre-dose, Day 1), Week 4 (Day 28), and 
Week 24 (Day 168). A PK sample will also be collected at Week 4 (Day 28) and at 
Week 24 (Day 168). At Week 12 (Day 84) and at the end of treatment Week 26 (Day 
168), the subject will also complete the PGI-C. A final visit will be conducted 2 weeks 
after the last application of study drug. Clinically significant abnormal laboratory 
parameters, and abnormal ECG noted at the previous visit, should be repeated at this 
visit. Comfort measures (e.g., topical analgesics and mechanical interference devices) 
may be used during all study blood collection events to reduce subject discomfort. 
A total of 8 scheduled visits will take place over approximately 26 weeks: Week 0 (Day 
1), Week 4 (Day 28), Week 8 (Day 56), Week 12 (Day 84), Week 16 (Day 112), Week 
20 (Day 140), Week 24 (Day 168), and Week 26 (Day 182). Subjects who prematurely 
discontinue study drug will complete the EOT (Week 24/Visit 7) visit.  
An internal Study Review Committee (SRC), comprising the Sponsor Medical Monitor, 
Lead Investigator and Contract Research Organization (CRO) Medical Monitor, will 
facilitate the management and identification of potential safety concerns, will assess 
whether revisions to the study protocol and/or consent are required, and will evaluate 
the overall progress of the study.  
Description of Test 
Article, Dosage, and 
Administration 
All subjects will receive active study drug. One dose of sofpironium bromide gel, 15% 
will be applied topically using the supplied applicator to each axilla QD at 
approximately the same time before bedtime for up to 24 weeks. Sofpironium bromide 
gel is packaged in airless, multi-dose, metered pump containers. Each administration of 
sofpironium bromide gel, 15% is ~0.67 mL and contains 86.5 mg of sofpironium 
bromide, for a total daily dose when applied to both axillae of 173 mg. 
Duration of Study 
Participation 
Each subject will participate in the study for up to 26 weeks: 
• 
Screening (Day 1)1 
• 
Treatment (24 weeks) 
• 
Follow-up (2 weeks after last dose) 
1 Subjects enrolled in Study BBI-4000-CL-105 opting to enroll in this extension study 
will continue receiving study drug in the extension study. The screening visit of Study 


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BBI-4000-CL-108 (Week 0/Day 1) and end of treatment (EOT) visit of Study BBI-
4000-CL-105 (Visit 4/Day 8) will be conducted simultaneously. 
Study Centers 
Up to 10 investigational sites in the United States (US) who participate in Study BBI-
4000-CL-105 will be eligible to participate in this study.  
Main Inclusion Criteria 
For a study subject to be evaluated for study participation:  
1. Written Informed Consent (including HIPAA) will be obtained from the 
Parent(s)/Legal Guardian(s) prior to the conduct of any study related 
procedures to permit participation of a minor in a clinical research study in 
accordance with federal and local laws. Additionally, assent from a minor 
child will be obtained in accordance with federal and local laws as well as in 
compliance with the recommendations of the approving Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC).  
Study subjects will be eligible for inclusion in the study if they meet all the following 
criteria at Screening/Enrollment (Week 0 [Day 1]) as applicable: 
2. Are male or female ≥9 to ≤17 years of age at the time of consent. 
3. Have enrolled and completed treatment in Study BBI-4000-CL-105 and met 
all inclusion/exclusion criteria, were compliant with study procedures (e.g., 
visits and PK sample collection), and did not experience any clinically 
significant AEs that would preclude safe continuation of study drug for up to 
an additional 24 weeks. 
4. Continue to be in generally good health based on Investigator's assessment 
(other than axillary hyperhidrosis), with no clinically significant laboratory 
abnormalities, co-morbidities or psychiatric conditions which, in the opinion 
of the Investigator, would place the subject at increased risk or would 
confound the objectives of the study. 
5. The Parent(s)/Legal guardian(s) and study subject are willing and able to 
follow all study-related procedures, including but not limited to application of 
study drug and venipuncture and are willing and able to return to the study 
clinic for required study visits. 
6. If female, must be willing to take monthly pregnancy tests during the study.  
7. Sexually active females must agree to use a medically acceptable method of 
contraception while receiving study drug. For purposes of this study, all 
female subjects are considered of childbearing potential as axillary 
hyperhidrosis generally occurs in post-pubescent individuals. Acceptable 
contraceptive methods include the following: 
a. 
Abstinence for the duration of the study or where partner is sterile 
(e.g., vasectomy) is an acceptable form of contraception. 
b. Hormonal contraception, including oral, injectable, or implantable 
methods started at least 2 months prior to screening, or 
c. 
Two forms of non-hormonal contraception, including intrauterine 
devices (IUD) (at least 1-week status post placement) and properly 
used barrier methods (e.g., male or female condoms, cervical 
cap/diaphragm, spermicidal agents, etc.). 
The Investigator will educate the subject regarding abstinence or contraception 
options and the correct and consistent use of effective contraceptive methods 
in order to successfully prevent pregnancy. 


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Main Exclusion Criteria 
A study subject will be excluded from the study if they meet any of the following 
criteria at Screening/Enrollment (Week 0 [Day 1]): 
1. In the Investigator’s opinion, any clinically significant systemic or local skin 
reaction related to use of the study drug. 
2. Subcutaneous tissue conditions of the axilla(e), (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). 
3. Has received any prohibited medication(s) or procedure(s) under Study BBI-4000-
CL-105 prior to Screening/Enrollment. 
4. Subject is pregnant, lactating or is planning to become pregnant during the study. 
5. Positive drug or alcohol screen while enrolled in Study BBI-4000-CL-105. 


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Statistical Analysis 
Sample Size  
Sample size is based on the planned enrollment under Study BBI-4000-CL-105. Up to 
24 subjects may participate in this study.  
 
Analysis Populations 
Two populations will be used for analysis: Safety and PK. The definition of these 
populations follows: 
• 
Safety Population: All enrolled subjects who applied at least one dose of 
study drug and have at least one post-baseline safety assessment 
• 
Pharmacokinetic Population: All enrolled subjects who applied at least one 
dose of study drug and have at least one quantifiable PK sample for analysis 
Primary Analysis  
Safety 
The Safety Population will be used for evaluation of safety assessments, which consists 
of reported AEs, application site local tolerability assessments, vital signs, physical 
examinations, 12-lead ECG, and laboratory measurements (hematology, chemistry, and 
urinalysis). Full details will be specified in the statistical analysis plan (SAP). 
Pharmacokinetics 
Individual plasma concentrations of sofpironium and BBI-4010 will be listed and 
summarized descriptively including arithmetic mean, standard deviation (SD), 
Coefficient of Variation (CV, %), median, minimum and maximum values. 
Full details of the analysis will be specified in the SAP. 
Exploratory 
Efficacy  
• 
The HDSM-Ax or HDSM-Ax, Child total score will be descriptively 
summarized for values at each visit and for changes from baseline. Baseline 
will be considered the Day 1 pre-dose evaluation under Study BBI-4000-CL-
105. 
• 
The HDSM-Ax or HDSM-Ax, Child Summary Questions; duration (No. 4) 
and severity (No. 5) will be descriptively summarized for values at each visit 
and for changes from baseline. Baseline will be considered the Day 1 pre-dose 
evaluation under Study BBI-4000-CL-105. 
• 
The PGI-S will be descriptively summarized for values at each visit and for 
changes from baseline. Baseline will be considered the Day 1 pre-dose 
evaluation, under Study BBI-4000-CL-105. 
• 
The PGI-C at Week 12 (Day 84) and Week 24 (Day 168), end of treatment 
will be summarized. 
Full details will be specified in the SAP.  
 


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SCHEDULE OF ACTIVITIES 
Description 
Screening/ 
Enrollment 
 
  
Treatment 
 End of 
Treatment/Early 
Termination 
End of Study 
 
Week 
Week 0 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24 
Week 26 
Study Day (±days)/ 
Visit  
Day 1/ 
Visit 1 
Day 28 (±3)/ 
Visit 2 
Day 56 (±5)/ 
Visit 3 
Day 84 (±5)/  
Visit 4 
Day 112 (±5)/ 
Visit 5 
 
Day 140 (±5)/ 
Visit 6 
 
 
Day 168 (±5)/ 
Visit 7 
 
Day 182 (±5)/ 
Visit 8 
Consent/Assent 
Refer to Section 6.1 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
Refer to Sections 5.1 and 5.2 
X 
  
 
 
 
 
 
 
Demographics 
Refer to Section 6.2 
X a 
 
 
 
 
 
 
 
Height/Weight 
Refer to Section 6.5 
X a 
 
 
 
 
 
 
 
Abbreviated Physical 
Examination 
Refer to Section 6.4 
X b 
X 
 
 
 
 
X 
X 
Medical/Medication History  
Refer to Section 6.3 
X b 
 
 
 
 
 
 
 
Vital Signs 
Refer to Section 6.7 
X b 
X  
X 
X 
X 
X 
X 
X 
HDSM-Ax and HDSM-Ax, 
Child  
Refer to Section 6.8 
X a 
X  
X 
X 
X 
X 
X 
X 
PGI-S  
Refer to Section 6.10 
X a,b 
X 
X 
X 
X 
X 
X 
X 
PGI-C  
Refer to Section 6.11 
 
 
 
X 
 
 
X 
 
Safety laboratory testing  
Refer to Section 6.12.4.2 
X a,b 
X 
 
 
 
 
X 
X d 
Pregnancy testing (females 
only) Refer to Section 6.12.4.1 
X b 
X 
X 
X 
X 
X 
X 
 


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Description 
Screening/ 
Enrollment 
 
  
Treatment 
 End of 
Treatment/Early 
Termination 
End of Study 
 
Week 
Week 0 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24 
Week 26 
Study Day (±days)/ 
Visit  
Day 1/ 
Visit 1 
Day 28 (±3)/ 
Visit 2 
Day 56 (±5)/ 
Visit 3 
Day 84 (±5)/  
Visit 4 
Day 112 (±5)/ 
Visit 5 
 
Day 140 (±5)/ 
Visit 6 
 
 
Day 168 (±5)/ 
Visit 7 
 
Day 182 (±5)/ 
Visit 8 
Pharmacokinetic sampling 
Refer to Section 6.12.5 
X b 
X c  
  
 
 
 
X c 
 
12-lead ECG 
Refer to Section 6.8 
X b 
X 
 
 
 
 
X 
X d 
Concomitant Medications 
Refer to Section 6.13 
X b 
X 
X 
X 
X 
X 
X 
X 
AE Assessment 
Refer to Section 10 
X b 
X 
X 
X 
X 
X 
X 
X 
Application Site Tolerability 
Assessment 
Refer to Section 6.6 
X b 
X 
X 
X 
X 
X 
X 
 
Dosing  
Refer to Sections 8.4 and 8.5 
and Study drug application 
and dosing diary card 
completion Refer to 
Appendix C 
  
 
Compliance  
Refer to Section 8.5 
X b 
X 
X 
X 
X 
X 
X 
 
Study Drug Dispensing 
Refer to Section 8.3 
X 
X 
X 
X 
X 
X 
 
 
ª  Baseline data (prior to first dose) collected under BBI-4000-CL-105 will be carried over to the current study. 
b  Data collected at End of Treatment (Day 8 [±1 day]) under BBI-4000-CL-105 will be carried over to the current study. 
c  Collection ≥12 hours from evening application of drug. 
d  Only collect if abnormal at Visit 7/Early Termination Visit. 


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TABLE OF CONTENTS 
AGREEMENT OF INVESTIGATOR COMPLIANCE ...........................................................3 
ABBREVIATIONS ...................................................................................................................4 
PROTOCOL SYNOPSIS ..........................................................................................................6 
SCHEDULE OF ACTIVITIES................................................................................................12 
1 
INTRODUCTION ........................................................................................................18 
1.1 
Background ..............................................................................................................18 
1.2 
Rationale ...................................................................................................................18 
1.3 
Risk / Benefit Assessment ........................................................................................18 
3 
STUDY OBJECTIVES AND ENDPOINTS ................................................................18 
3.1 
Objectives .................................................................................................................18 
3.1.1 
Primary Objectives ..............................................................................................18 
3.1.1.1 
Safety.................................................................................................................18 
3.1.1.2 
Pharmacokinetics ..............................................................................................18 
3.1.2 
Exploratory Objectives ........................................................................................19 
3.2 
Criteria for Evaluation ..............................................................................................19 
3.2.1 
Primary Endpoints ...............................................................................................19 
3.2.1.1 
Safety.................................................................................................................19 
3.2.1.2 
Pharmacokinetics ..............................................................................................19 
3.2.2 
Exploratory Endpoints .........................................................................................19 
4 
STUDY DESIGN ..........................................................................................................20 
4.1 
General Description ..................................................................................................20 
4.2 
Screening and Enrollment ........................................................................................21 
4.3 
Screen Failure ...........................................................................................................21 
4.4 
Completion ...............................................................................................................21 
4.5 
Early Termination (ET) ............................................................................................21 
4.5.1 
Criteria for Premature Discontinuation ...............................................................21 
4.5.1.1 
Discontinuation from Treatment .......................................................................21 
4.5.1.2 
Discontinuation from Study ..............................................................................22 
4.5.1.3 
Lost to Follow-up ..............................................................................................22 
4.5.1.4 
Subject Replacement .........................................................................................22 
4.6 
Safety Oversight .......................................................................................................22 
4.6.1 
Study Review Committee (SRC) .........................................................................22 
4.6.2 
Investigator ..........................................................................................................22 
5 
STUDY SUBJECT SELECTION .................................................................................23 
5.1 
Inclusion Criteria ......................................................................................................23 
5.2 
Exclusion Criteria .....................................................................................................24 


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6 
DESCRIPTION OF STUDY PROCEDURES .............................................................24 
6.1 
Obtaining Informed Consent ....................................................................................24 
6.1.1 
Written Parental/Legal Guardian Consent ...........................................................24 
6.1.2 
Minimum Federal Requirements for Consent .....................................................25 
6.1.3 
When Parents/Legal Guardians Disagree ............................................................25 
6.1.4 
Assent ..................................................................................................................25 
6.1.5 
Documenting the Consent/Assent Process ..........................................................25 
6.2 
Demographics ...........................................................................................................25 
6.3 
Histories ...................................................................................................................25 
6.3.1 
General Medical/Surgical and Social History .....................................................25 
6.3.2 
History – Hyperhidrosis ......................................................................................26 
6.3.3 
Medication History ..............................................................................................26 
6.4 
Abbreviated Physical Examination ..........................................................................26 
6.5 
Height and Weight ...................................................................................................26 
6.6 
Application Site Tolerability Assessment ................................................................26 
6.7 
Vital Signs ................................................................................................................27 
6.7.1 
Temperature and Respiratory Rate ......................................................................27 
6.7.2 
Seated Blood Pressure and Heart Rate ................................................................27 
6.8 
Twelve-Lead Electrocardiogram (ECG) ..................................................................27 
6.9 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) .............................27 
6.10 
Patient Global Impression of Severity (PGI-S) ........................................................28 
6.11 
Patient Global Impression of Change (PGI-C) ........................................................28 
6.12 
Laboratory Testing ...................................................................................................28 
6.12.1 
Testing Facilities .................................................................................................28 
6.12.2 
Sample Collection and Blood Volumes ..............................................................28 
6.12.3 
Sample Identification ...........................................................................................28 
6.12.4 
Screening and Safety Laboratory Testing ...........................................................28 
6.12.4.1 
Pregnancy Testing .............................................................................................28 
6.12.4.2 
Routine Safety Laboratory Testing ...................................................................29 
6.12.5 
Pharmacokinetics .................................................................................................29 
6.13 
Concomitant Medications ........................................................................................29 
6.13.1 
General ................................................................................................................29 
6.13.2 
Concomitant Medication Restrictions .................................................................30 
6.14 
Prevention of Pregnancy during the Study ...............................................................30 
6.14.1 
Instructions for Female Subjects .........................................................................30 
6.15 
Lifestyle Guidelines .................................................................................................30 
7 
STUDY VISITS ............................................................................................................31 
7.1 
Screening/Enrollment (Week 0 [Day 1]) .................................................................31 
7.2 
Treatment: Week 4 (Day 28 [±3 days]) through Week 24 (Day 168 [±5 days]) .....32 
7.3 
End of Treatment/Early Termination: Week 24 (Day 168 [±5 days]) .....................33 


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7.4 
End of Study: Week 26 (Day 182 [±5 days]) ...........................................................33 
7.5 
Unscheduled Additional Visit(s) ..............................................................................34 
8 
INVESTIGATIONAL PRODUCT ...............................................................................34 
8.1 
Formulation, Packaging and Labelling ....................................................................34 
8.1.1 
Formulation .........................................................................................................34 
8.1.2 
Packaging and Labeling ......................................................................................34 
8.2 
Storage ......................................................................................................................34 
8.3 
Dispensing ................................................................................................................34 
8.4 
Dosing ......................................................................................................................35 
8.5 
Compliance ...............................................................................................................35 
8.6 
Study Drug Accountability .......................................................................................35 
8.7 
Blinding ....................................................................................................................35 
8.8 
Breaking the Study Blind .........................................................................................35 
9 
PROTOCOL VIOLATIONS ........................................................................................35 
10 
ADVERSE EVENTS ....................................................................................................36 
10.1 
Safety Evaluations ....................................................................................................36 
10.2 
Adverse Events .........................................................................................................36 
10.2.1 
Definition of Adverse Events ..............................................................................36 
10.2.2 
Documentation and Monitoring Adverse Events ................................................37 
10.2.3 
Assessment of Adverse Events ............................................................................37 
10.3 
Serious Adverse Events ............................................................................................39 
10.3.1 
Definition and Reporting Procedures ..................................................................39 
10.3.2 
Reporting Serious Adverse Events to Regulatory Agencies ...............................39 
10.4 
Follow-up of Adverse Events and Laboratory Test Abnormalities .........................40 
10.5 
Pregnancy Reporting ................................................................................................40 
10.5.1 
Definition of Female of Childbearing Potential ..................................................40 
10.5.2 
Testing and Acceptable Methods of Birth Control ..............................................40 
10.5.3 
Time Period for Collecting Pregnancy Information ............................................40 
10.5.4 
Action to be Taken if Pregnancy Occurs .............................................................40 
11 
DATA ANALYSIS AND STATISTICAL METHODS ..............................................41 
11.1 
Sample Size Determination ......................................................................................41 
11.2 
Analysis Populations ................................................................................................41 
11.3 
Statistical Analysis ...................................................................................................41 
11.3.1 
General Statistical Methodology .........................................................................41 
11.3.2 
Demographics, Baseline Characteristics, Medical History, Hyperhidrosis 
History, and Concomitant Medications ...............................................................41 
11.3.3 
Treatment Compliance ........................................................................................41 
11.3.4 
Drug Exposure .....................................................................................................41 
11.4 
Primary Analysis ......................................................................................................42 
11.4.1 
Safety ...................................................................................................................42 


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11.4.2 
Pharmacokinetics .................................................................................................42 
11.5 
Exploratory Analysis ................................................................................................43 
11.6 
Interim ......................................................................................................................43 
12 
DATA COLLECTION, RETENTION AND MONITORING .....................................43 
12.1 
Data Collection Instruments .....................................................................................43 
12.2 
Data Management Procedures ..................................................................................44 
12.2.1 
Data Quality Control and Reporting ....................................................................44 
12.2.2 
Data Entry ............................................................................................................44 
12.2.3 
Medical Information Coding ...............................................................................44 
12.2.4 
Data Validation ....................................................................................................44 
12.3 
Archival of Data .......................................................................................................44 
12.4 
Availability and Retention of Investigational Records ............................................44 
12.5 
Monitoring ................................................................................................................45 
12.6 
Subject Confidentiality .............................................................................................45 
12.7 
Retained Blood Samples ..........................................................................................45 
13 
ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS .................45 
13.1 
Protocol Amendments ..............................................................................................45 
13.2 
Institutional Review Boards and Independent Ethics Committees ..........................46 
13.3 
Informed Consent Form – General Provisions .........................................................46 
13.4 
Publications ..............................................................................................................47 
13.5 
Clinical Trials Registration ......................................................................................47 
14 
SPONSOR DISCONTINUATION CRITERIA ...........................................................47 
15 
REFERENCES ..............................................................................................................48 
APPENDIX A  
HDSM-AX, CHILD (≥9 TO <12 YEARS OF AGE) ................................49 
APPENDIX B  
HDSM-AX (≥12 YEARS OF AGE) ..........................................................51 
APPENDIX C  
STUDY DRUG APPLICATION AND SUBJECT INSTRUCTIONS 
AND DOSING DIARY CARD .................................................................54 
APPENDIX D  
EXAMPLES OF POTENT INHIBITORS CYP3A AND CYP2D6 ..........58 
APPENDIX E 
EXAMPLES OF POTENT INHIBITORS OF OCT-2/MATE1/MATE2 
TRANSPORTERS .....................................................................................59 
APPENDIX F  
APPLICATION SITE TOLERABILITY ASSESSMENTS ......................60 


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1 
INTRODUCTION 
1.1 
Background  
Sofpironium bromide (BBI-4000) is a novel soft-anticholinergic ester analog of 
glycopyrrolate in development for the topical treatment of primary axillary hyperhidrosis.  
1.2 
Rationale  
The pediatric pharmacokinetic and safety study (BBI-4000-CL-105) that precedes this long-
term safety extension study, is a short treatment duration (7 days [±1 day]) PK study. The 
purpose of this study is to collect additional safety and tolerability information on children 
and adolescents following once daily sofpironium bromide gel, 15% treatment for up to 24 
wks. Furthermore, subjects enrolled in Study BBI-4000-CL-105 may only begin to perceive 
improvement of symptoms near its conclusion. Therefore, subjects who complete Study BBI-
4000-CL-105 will be allowed the opportunity to participate in this long-term extension study 
(i.e., 24 weeks of treatment) in which they may potentially experience additional clinical 
benefit from sofpironium bromide gel, 15%. The data collected will further inform enhance 
the pediatric safety and tolerability profile of the study drug. 
1.3 
Risk / Benefit Assessment 
The results to date of the clinical program support the safe use of sofpironium bromide gel, 
15% for the treatment of primary axillary hyperhidrosis. Ten clinical studies have been 
conducted with sofpironium bromide gel exposing over 700 adult subjects to the active 
ingredient: two Phase 1 studies in healthy adults, four Phase 1 and three Phase 2 studies in 
adults with primary axillary hyperhidrosis, and a Phase 2 study in adults with primary palmar 
hyperhidrosis.  
Sofpironium bromide has consistently demonstrated low incidence of treatment-emergent 
adverse events (TEAEs) following daily application for periods of time up to 6 weeks. Most 
AEs have been mild and transient, with all resolving after treatment discontinuation. A long-
term safety study (BBI-4000-CL-303) to evaluate the safety and tolerability of sofpironium 
bromide gel, 15% in subjects ≥12 years of age has been initiated and is ongoing at this time.  
3 
STUDY OBJECTIVES AND ENDPOINTS 
3.1 
Objectives 
3.1.1 Primary Objectives 
3.1.1.1 Safety 
To assess the long-term safety and tolerability of sofpironium bromide gel, 15% applied 
topically once daily for up to 24 weeks in children and adolescent subjects, >9 to ≤17 years 
of age, with axillary hyperhidrosis.  
3.1.1.2 Pharmacokinetics 
To assess the systemic exposure (Ctrough) of sofpironium and its primary metabolite (BBI-
4010) following topical application of ~0.67 mL of sofpironium bromide gel, 15% applied 
topically to each axilla, once daily (QD) for up to 24 weeks. 


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3.1.2 Exploratory Objectives 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) and Hyperhidrosis 
Disease Severity Measure-Axillary, Child (HDSM-Ax, Child) in pediatric subjects, ≥9 
to ≤17 years of age, with axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Summary Questions; 
duration (No. 4) and severity (No. 5) in pediatric subjects, ≥9 to ≤17 years of age, with 
axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on Patient 
Global Impression of Severity (PGI-S) in pediatric subjects, ≥9 to ≤17 years of age, 
with axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on Patient 
Global Impression of Change (PGI-C) in pediatric subjects, ≥9 to ≤17 years of age, 
with axillary hyperhidrosis 
3.2 
Criteria for Evaluation 
3.2.1 Primary Endpoints 
3.2.1.1 Safety 
• 
Incidence and severity of application site burning, itching, stinging, scaling and 
erythema  
• 
Incidence and severity of all AEs and their relationship to study drug 
• 
Incidence of clinically meaningful change from baseline in safety laboratory 
parameters, 12-lead electrocardiograms (ECGs) and vital signs 
• 
Proportion of subjects who discontinue treatment due to an AE 
3.2.1.2 Pharmacokinetics 
• 
Determination of plasma concentrations (Ctrough) of sofpironium, and BBI-4010 at 
Week 4 and Week 24 (end of treatment) following 24 weeks of QD topical application 
of sofpironium bromide gel, 15%. 
3.2.2 Exploratory Endpoints 
• 
Change of HDSM-Ax (≥12 years of age) or HDSM-Ax, Child (≥9 to <12 years of age) 
from baseline to end of treatment 
• 
Change of HDSM-Ax Summary Questions; duration (No. 4) and severity (No. 5) from 
baseline to end of treatment. 
• 
Change of PGI-S from baseline to end of treatment 
• 
PGI-C at Week 12 (Day 84) and end of treatment 


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4 
STUDY DESIGN 
4.1 
General Description 
This multi-center, open-label extension study will evaluate the long-term safety, tolerability, 
and pharmacokinetics of sofpironium bromide gel, 15%, when applied QD for up to 6 
months in pediatric subjects ≥9 years to ≤17 years of age with axillary hyperhidrosis 
previously enrolled in Study BBI-4000-CL-105.  
Following completion of the initial PK and safety study (Study BBI-4000-CL-105), subjects 
will be provided the opportunity to enter this 6-month open-label extension study. Subjects 
will be screened for eligibility at Day 8 of Study BBI-4000-CL-105 (last PK sample 
collection under BBI-4000-CL-105 study). Therefore, for participating subjects, the final 
treatment visit (i.e., Day 8/Visit 4) of Study BBI-4000-CL-105 and the Screening/Enrollment 
visit (i.e., Week 0 [Day 1]) of Study BBI-4000-CL-108 (long-term extension study) will take 
place simultaneously. 
Subjects (parent/guardian) will be dispensed one container of sofpironium bromide gel, 15% 
each month at Visits 1-6. Subjects (and parent/guardian) will be instructed on the correct 
application procedure for sofpironium bromide gel, 15% (to be applied QD before bedtime to 
both axilla for up to 24 weeks). 
Vital signs, review of concomitant medications, assessment of AEs, completion of patient-
reported outcomes (HDSM-Ax or HDSM-Ax, Child, and PGI-S), and urine pregnancy tests 
(UPT) for all females will be done each visit. Application site tolerability will be assessed at 
all visits through the end of treatment (EOT) at Week 24 (Day 168 [±5 days]). Blood and 
urine for safety testing will be collected and analyzed at Week 4 (Day 28 [±3 days]) and 
Week 24 (Day 168 [±5 days]) for routine hematology, chemistry, and urinalysis parameters. 
ECGs will be assessed at Week 0 (pre-dose, Day 1), Week 4 (Day 28 [±3 days]), and Week 
24 (Day 168[ ±5 days]). A PK sample will also be collected at Week 4 (Day 28 [±3 days]) 
and at Week 24 (Day 168 [±5 days]). At Week 12 (Day [84 ±5 days]) and at the end of 
treatment at Week 24 (Day [162 ±5 days]), the subject will also complete the PGI-C. A final 
visit will be conducted 2 weeks after the last application of study drug. Clinically significant 
abnormal laboratory parameters, and abnormal ECG noted at the previous visit, should be 
repeated at this visit. Comfort measures (e.g., topical analgesics and mechanical interference 
devices) may be used during all study blood collection events to reduce subject discomfort. 
A total of 8 scheduled visits will take place over approximately 26 weeks: Week 0 (Day 1), 
Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [±5 days]), Week 12 (Day 84 [±5 days]), Week 
16 (Day 112 [±5 days]), Week 20 (Day 140 [±5 days]), Week 24 (Day 168 [±5 days]), and 
Week 26 (Day [182 ±5 days]). Subjects who prematurely discontinue study drug will 
complete the EOT (Week 24/Visit 7) visit.  
An internal Study Review Committee (SRC), comprising the Sponsor Medical Monitor, Lead 
Investigator and Contract Research Organization (CRO) Medical Monitor, will facilitate the 
management and identification of potential safety concerns, will assess whether revisions to 
the study protocol and/or consent are required, and will evaluate the overall progress of the 
study. 


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Figure 1 
Study Schematic 
 
4.2 
Screening and Enrollment 
Subjects enrolled in this study will be males and females, >9 to ≤17 years of age, with 
axillary hyperhidrosis who participated and completed treatment in Study BBI-4000-CL-105. 
Up to 24 subjects may participate in this study. 
4.3 
Screen Failure 
A subject who has been screened but subsequently fails to meet the inclusion/exclusion 
criteria prior to receipt of study drug in this study will be deemed a screen failure.  
4.4 
Completion 
Each subject will participate in the study for up to approximately 26 weeks, from the time the 
informed consent form (ICF) is signed/assent provided (Visit 1) through the final visit (Week 
26 [Day 182 (±5 days)]).  
4.5 
Early Termination (ET) 
A subject or the subject’s parent/guardian may withdraw the subject from treatment or from 
the study at any time upon request or the subject may be withdrawn at any time at the 
discretion of the Investigator or Sponsor for safety, behavioral, or administrative reasons.  
4.5.1 Criteria for Premature Discontinuation 
4.5.1.1 Discontinuation from Treatment 
A subject must be permanently discontinued from the study drug for any of the following 
reasons: 
• 
The subject becomes pregnant. 
• 
Allergic or adverse reaction to the study drug. 
• 
Clinically significant AE, which in the opinion of the Investigator, or SRC, would put 
the subject at unnecessary risk if dosing was continued. 
• 
The subject’s axillary hyperhidrosis worsens and requires alternative or supplemental 
medication during the study. 


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If a subject is discontinued from treatment, he or she should continue to be followed in the 
study per the SCHEDULE OF ACTIVITIES. If subject refuses to stay in the study, then he 
or she will be encouraged to complete the Early Termination Visit 7 study procedures. 
4.5.1.2 Discontinuation from Study 
A subject must be discontinued from study drug and from the study for the following reason: 
• 
The subject withdraws consent. From the time consent is withdrawn, no additional 
data should be collected. However, the Sponsor may retain and continue to use data 
collected before such withdrawal of consent.  
A subject may be discontinued from the study drug or from the study for the following 
reason: 
• 
The subject requests withdrawal from the study. For the safety of the subject, if 
withdrawal is requested, the subject should be encouraged to complete the Early 
complete the Early Termination Visit 7 study procedures. 
4.5.1.3 Lost to Follow-up 
A subject is considered to have been lost to follow-up if he/she [subject or parent/legal 
guardian] cannot be contacted by the Investigator (or designee) after 3 documented attempts. 
The Investigator (or designee) will document efforts to attempt to reach the subject/ 
parent/guardian. The end of participation for a subject lost to follow-up is documented as the 
date of the last visit. 
4.5.1.4 Subject Replacement 
Subjects who prematurely discontinue will not be replaced.  
4.6 
Safety Oversight 
4.6.1 Study Review Committee (SRC) 
An internal SRC, comprising the Sponsor Medical Monitor, Lead Investigator and CRO 
Medical Monitor, will facilitate the management and identification of potential safety 
concerns and will assess whether revisions to the study protocol and/or consent are required 
and will evaluate the overall progress of the study. 
4.6.2 Investigator 
The Investigator must have access and be available to promptly review the results of all 
safety assessments (i.e., clinical laboratory testing), ECG results, vital signs and AEs 
including application site assessment information throughout the study. Safety assessments 
must be promptly entered into the Electronic Data Capture (EDC) system (if possible, within 
48 hours of notification of event). Clinical laboratory data will be evaluated by the 
Investigator and clinical relevance will be assessed for abnormal values and the assessment 
will be documented on the laboratory report. A copy of the reports will be maintained as part 
of the source documentation. 


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5 
STUDY SUBJECT SELECTION 
5.1 
Inclusion Criteria 
For a study subject to be evaluated for study participation:  
 Written Informed Consent (including HIPAA) will be obtained from the 
Parent(s)/Legal Guardian(s) prior to the conduct of any study related procedures to 
permit participation of a minor in a clinical research study in accordance with federal 
and local laws. Additionally, assent from a minor child will be obtained in accordance 
with federal and local laws as well as in compliance with the recommendations of the 
approving Institutional Review Board (IRB)/Institutional Ethics Committee (EC).  
Study subjects will be eligible for inclusion in the study if they meet all the following criteria 
at Screening/Enrollment (Week 0 [Day 1]) as applicable: 
 Are male or female ≥9 to ≤17 years of age at the time of consent. 
 Have enrolled and completed treatment in Study BBI-4000-CL-105 and met all 
inclusion/exclusion criteria, were compliant with study procedures (e.g., visits and PK 
sample collection) and did not experience any clinically significant AEs that would 
preclude safe continuation of study drug for up to an additional 24 weeks. 
 Continue to be in generally good health based on Investigator's assessment (other 
than axillary hyperhidrosis), with no clinically significant laboratory abnormalities, 
co-morbidities or psychiatric conditions which, in the opinion of the Investigator, 
would place the subject at increased risk or would confound the objectives of the 
study. 
 The Parent(s)/Legal guardian(s) and study subject are willing and able to follow all 
study-related procedures, including but not limited to application of study drug and 
venipuncture and are willing and able to return to the study clinic for required study 
visits. 
 If female, must be willing to take monthly pregnancy tests during the study.  
 Sexually active females must agree to use a medically acceptable method of 
contraception while receiving study drug. For purposes of this study, all female 
subjects are considered of childbearing potential as axillary hyperhidrosis generally 
occurs in post-pubescent individuals. Acceptable contraceptive methods include the 
following: 
a. Abstinence for the duration of the study or where partner is sterile (e.g., 
vasectomy) is an acceptable form of contraception. 
b. Hormonal contraception, including oral, injectable, or implantable methods 
started at least 2 months prior to screening, or 
c. Two forms of non-hormonal contraception, including intrauterine devices 
(IUD) (at least 1-week status post placement) and properly used barrier 
methods (e.g., male or female condoms, cervical cap/diaphragm, spermicidal 
agents, etc.). 
The Investigator will educate the subject regarding abstinence or contraception options and 
the correct and consistent use of effective contraceptive methods in order to successfully 
prevent pregnancy. 


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5.2 
Exclusion Criteria 
A study subject will be excluded from the study if they meet any of the following criteria 
at Screening/Enrollment (Week 0 [Day 1]). 
 In the Investigator’s opinion, any clinically significant systemic or local skin reaction 
related to use of the study drug. 
 Subcutaneous tissue conditions of the axilla(e), (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). 
 Has received any prohibited medication(s) or procedure(s) under Study BBI-4000-
CL-105 prior to Screening/Enrollment. 
 Subject is pregnant, lactating or is planning to become pregnant during the study. 
 Positive drug or alcohol screen while enrolled in Study BBI-4000-CL-105. 
6 
DESCRIPTION OF STUDY PROCEDURES  
A description of study procedures and frequency are listed in the SCHEDULE OF 
ACTIVITIES and is provided within the content of this protocol.  
6.1 
 Obtaining Informed Consent 
6.1.1 Written Parental/Legal Guardian Consent 
Adequate provisions must be made for soliciting the permission of the subject’s parent(s) or 
legally authorized representative/guardian. If a subject turns 18 years of age during the 
course of the study, written informed consent will be obtained from the subject at the next 
visit. 
The process for obtaining oral and/or written assent for children and adolescents is similar to 
that of obtaining consent for adults. An effective informed consent process involves at 
minimum these elements:  
• Conducting the process in a manner and location that ensures privacy; 
• Giving adequate information about the study in a language understandable to the 
parent/legal guardian and child/adolescent; 
• Providing adequate opportunity for the parent/legal guardian and child/adolescent to 
consider all options; 
• Responding to the parent(s)/legal guardian(s) and child’s/adolescent’s questions; 
• Ensuring the parent/legal guardian and child/adolescent has understood the 
information provided; 
• Obtaining the parent/legal guardian and child/adolescent voluntary agreement to 
participate, and  
• Continuing to provide information to parent(s)/legal guardian(s), child/adolescent as 
new information regarding this research program becomes available that may affect 
their willingness to continue in this study. 


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6.1.2 Minimum Federal Requirements for Consent 
The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) will determine 
the permissions (one or both parents/legal guardian(s)) required for participation of a minor 
in this study based on level of risk (e.g., minimal or greater than minimal).  
6.1.3 When Parents/Legal Guardians Disagree  
If there are two parents/legal guardians available to give permission but they disagree about 
allowing their child to participate in the study, the child may not be enrolled unless that 
disagreement can be resolved. This applies even if only one parent’s (guardian’s) signature is 
required. When both parents (guardians) are involved in the decision, they must agree for the 
child to be enrolled. If a parent who was not involved or available for the original consent 
later becomes involved or available, the two parents (guardians) must then agree. 
6.1.4 Assent 
The Investigator should carefully consider and propose adequate provisions for obtaining 
assent of children and adolescents prior to their participating in research. In general, assent is 
usually obtained from a child ≥ 7 years of age, however the approving IRB/IEC will 
determine whether or how assent will be obtained. The child should be provided with 
essential information and asked if they wish to participate in the research study.  
6.1.5 Documenting the Consent/Assent Process 
Consent/Assent MUST be obtained and documented PRIOR to initiation of any study 
procedures. The Principal Investigator or his/her approved designee must explain the nature 
of the study and associated risks to the parent(s)/legal guardian and study subject. The 
date/time that the informed consent is signed, a brief description of the consent/assent 
process (e.g., questions asked by the subject), and the name of the individual who obtained 
consent will be recorded in the source record. A copy of the signed informed consent should 
be provided to the parent(s)/legal guardian. Depending on the approving IRB and local 
requirements, an assent form may be included as part of the consent and may or may not be 
required to be signed by the child. Investigators must adhere to their local requirements for 
proper documentation of consent/assent. A summary of assent procedures for execution of 
this study must be maintained in the Investigator Essential Regulatory File. It is the 
responsibility of the Principal Investigator to ensure that any individual delegated the 
responsibility for obtaining consent/assent are familiar and adhere to the applicable 
consent/assent requirements. 
6.2 
Demographics  
Subject demographic information will be recorded at Screening/Enrollment (Week 0 [Day 
1]). Demographic information will include date of birth, gender (at the time of birth), race, 
and ethnicity. Findings will be documented in the source documentation and the eCRF.  
6.3 
Histories 
6.3.1 General Medical/Surgical and Social History 
Relevant medical and surgical history will be recorded at Screening/Enrollment (Week 0 
[Day 1]) and will include medical diagnoses, major surgical procedures within the last 3 


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years. Social history (i.e., tobacco, drug, and alcohol use) and allergies (i.e., food, 
medications and environmental) will also be recorded at screening. Findings will be 
documented in the source documentation and the eCRF. 
6.3.2 History – Hyperhidrosis 
The parent/guardian and subject will provide historical information pertaining to the 
diagnosis of axillary hyperhidrosis, including date of diagnosis. 
6.3.3 Medication History  
Medications taken within the last month (30 days) prior to first dose of sofpironium bromide 
gel, 15% under Study BBI-4000-CL-105 and within 1 week prior to Screening/Enrollment 
(Week 0 [Day 1]) will be recorded in the source document and on the eCRF. Also refer to 
Section 6.13 concomitant medications and restrictions for additional information. 
6.4 
Abbreviated Physical Examination 
The abbreviated physical examination will include an examination of general appearance, 
skin (including specific evaluation of axillary vaults), lungs, and heart. Additional systems 
will be evaluated as needed. Physical exam findings must be recorded in the source 
documentation and include the date and name of the individual conducting the examination. 
Physical examinations must be performed by an individual licensed to conduct standard 
physical examinations. An examination will be done at every visit. 
6.5 
Height and Weight 
Height and weight will be collected at Baseline, prior to first dose, collected under BBI-
4000-CL-105, and will be carried over to the current study. 
6.6 
Application Site Tolerability Assessment 
Application site tolerability assessments will be evaluated through assessment of symptoms 
at the drug-application site. These assessments are to be performed for each axilla 
individually. Subject assessments will be made prior to the Investigator assessments 
(Appendix F).  
Subject Local Tolerability Assessments: Subjects will be queried about whether any 
symptoms of burning, stinging, or itching occurred at the drug-application site within the 
previous 24 hours and further whether any such symptoms persisted longer than 1 hour 
following study drug application. Standardized scales will be used to describe specifically the 
severity of any burning, stinging or itching (Appendix F).  
Investigator Local Tolerability Assessments: Investigators will observe for the existence of 
any significant local symptoms of scaling or erythema at the drug-application site. 
Significant local symptoms are defined as those not ordinarily observed following 
application of a topical product. Standardized scales will be used to describe specifically the 
severity of any erythema or scaling (Appendix F).  
Local tolerability signs and symptoms that result in the subject’s requiring a concomitant 
therapy, interruption of treatment, or discontinuation from the study, will also be reported as 
an AE.  


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6.7 
Vital Signs  
Vital signs will be taken at every visit. 
6.7.1 Temperature and Respiratory Rate 
Temperature (oral or oral equivalent) and respiratory rate will be recorded once at each 
scheduled time point. Findings will be recorded in the source documentation and in the 
eCRF. 
6.7.2 Seated Blood Pressure and Heart Rate 
Blood pressure should always be measured on the SAME arm (location should be 
documented) and with an appropriately sized (e.g., pediatric cuff) blood pressure cuff (that 
should be the same sized cuff throughout the study) for accurate comparison of readings over 
time. Position is critical for accurate BP measurements. Therefore, when the BP is measured, 
the arm (cuff) should be at the level of the heart. When seated, feet should be flat on the floor 
(if possible) with back supported and arm supported at the level of the heart (e.g., resting on a 
table). Blood pressure (systolic/diastolic) and HR will be assessed after the study subject has 
rested in a seated position for at least five (5) minutes.  
It is important that vital signs be taken either before a meal, or at least 30 minutes after a 
meal or consuming caffeine containing products. 
6.8 
Twelve-Lead Electrocardiogram (ECG) 
Investigative sites will use a calibrated ECG machine to obtained ECGs. The ECG paper 
speed will be set to 25 mm/second. Site personnel must assess the quality of the ECG while 
the subject is still at the investigative site in the event that an additional ECG needs to be 
performed (i.e., if artefact is present). Subject QT intervals will be reported as corrected for 
HR according to the Fridericia Formula (QTcF).  
TWO ORIGINAL IDENTICAL ECGs should be printed (1 source and 1 for Sponsor) and 
labelled with Subject ID, and collection timepoint. The Investigator will read, provide 
interpretation, and sign and date the source document ECG.  
For younger children who have difficulty lying still, the parent/guardian (caregiver) should 
practice prior to the Day 1 study visit. It is suggested that parents/guardians be instructed on 
the use of a timer to help the child understand how long to hold still. If possible, have the 
subject rest quietly for at least 10 minutes.  
ECGs will be done at Week 0 (Day 1) [data to carry over from Day 8/Visit 4 of Study BBI-
4000-CL-105], Week 4 (Day 28 [±3 days]), Week 24 (Day 168 [±5 days]) and Week 26 (Day 
182 [±5 days]), if abnormal at Week 24. 
6.9 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) 
The HDSM-Ax (Appendix B) was developed to determine the severity of excessive sweating 
in patients ≥12 years of age with primary axillary hyperhidrosis. The HDSM-Ax is a well-
developed, validated measure of patient-reported signs and symptoms that quantifies changes 
in symptom severity in response to treatment (Kirsch, 2018). A child version (refer to 
Appendix A) suitable for use in children ≥9 to <12 years of age (HDMX-Ax, Child), will 
also be used in this study. The subject will be asked to complete the first 5 questions. 
Measure will be assessed at Week 0 (pre-dose Day 1), Week 4 (Day 28 [±3 days]), Week 8 


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(Day 46 [±5 days]), Week 12 (Day 84 [±5 days]), Week 16 (Day 112 [±5 days]) Week 20 
(Day 140 [±5 days]), and Week 24 (Day 168 [±5 days]) and Week 26 (Day 182 [±5 days]).  
6.10 Patient Global Impression of Severity (PGI-S) 
All subjects will be asked to complete one question pertaining to the severity of underarm 
sweating over the past week (refer to Appendix A, No. 6 and Appendix B, No. 6). Measure 
will be assessed at Week 0 (pre-dose Day 1), Week 4 (Day 28 [±3 days]), Week 8 (Day 46 
[±5 days]), Week 12 (Day 84 [±5 days]), Week 16 (Day 112 [±5 days]) Week 20 (Day 140 
[±5 days]), Week 24 (Day 168 [±5 days]) and Week 26 (Day 182 [±5 days]). 
6.11 Patient Global Impression of Change (PGI-C) 
All subjects will be asked to complete one question pertaining to the overall change in 
underarm sweating since the subject started the study drug (refer to Appendix A, No. 7 and 
Appendix B, No. 7). Measure will be assessed at Week 12 (Day 84 [±5 days]) and the end of 
treatment, Week 24 (Day 168 [±5 days]).  
6.12 Laboratory Testing 
6.12.1 Testing Facilities 
Blood samples for routine safety laboratory testing will be analyzed by a centralized 
laboratory that is certified under the Clinical Laboratory Improvement Act (CLIA).  
6.12.2 Sample Collection and Blood Volumes 
Blood samples will be collected via venipuncture. Measures should be taken to minimize 
discomfort during sample collection including but not limited to diversion or use of a topical 
anesthetic (supplied).  
Total blood volume (TBV) is related to body weight. The TBV of a child is approximately 
75-80 mL/kg. Existing guidelines for blood sample volume limits (ranging from 1–5% of 
total blood volume within 24 hours and up to 10% of total blood volume over 8 weeks) are 
consistent with the limited evidence available on “minimal risk” to children (Howie, 2011).  
In this study, the smallest volume of blood possible will be collected for analysis of safety 
and PK. Blood samples are scheduled to be collected Week 4 (Day 28 [±3 days]) and Week 
24 (Day 168 [±5 days]). Approximately 6 mL will be collected for safety, and approximately 
2 mL for PK at each collection time point. Laboratory tests may be repeated as clinically 
indicated at Week 26 (Day 182 [±5 days]).  
6.12.3 Sample Identification  
Blood samples will be labeled with the subject ID, sample collection date/time, and sample 
type. The Sponsor will not have any information that would identify the study subject.  
6.12.4 Screening and Safety Laboratory Testing 
6.12.4.1 Pregnancy Testing  
A pregnancy test is required for all female subjects. A UPT (local) will be done at all visits 
through Week 24 (Day 168 [±5 days]). Testing will be performed utilizing CLIA waived 
methodology. Testing supplies will be provided by the Sponsor to be used locally at the site. 


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6.12.4.2 Routine Safety Laboratory Testing  
The following safety laboratory panel will be collected at Week 0 (Day 1) [data to carry over 
from Day 8/Visit 4 of Study BBI-4000-CL-105], Week 4 (Day 28 [±3 days]), and Week 24 
(Day 168 [±5 days]). Laboratory tests may be repeated as clinically indicated at Week 26 
(Day 182 [±5 days]) and analyzed by a central reference laboratory. Safety laboratory 
samples will be collected in accordance with the Schedule of Activities. Additional samples 
may be collected and analyzed as clinically indicated. Details regarding collection, shipping 
and reporting of results will be provided in the Laboratory Reference Manual. 
Table 1 
Safety Laboratory Panel 
Hematology 
Platelet Count  
RBC Indices: 
Automated WBC Differential: 
Red blood cell (RBC) 
Count 
Mean corpuscular volume (MCV) 
Neutrophils 
White blood cell (WBC) 
Count (absolute)  
Mean corpuscular hemoglobin 
(MCH) 
Lymphocytes 
Reticulocyte Count 
Mean corpuscular hemoglobin 
concentration (MCHC) 
Monocytes 
Hemoglobin 
 
Eosinophils 
Hematocrit 
 
Basophils 
Clinical Chemistry 
Blood urea nitrogen 
(BUN) 
Chloride 
Alkaline phosphatase 
Creatinine 
Aspartate aminotransferase (AST)  
Total and direct bilirubin 
Sodium 
Alanine aminotransferase (ALT) 
 
Potassium 
Gamma-glutamyl transferase (GGT) 
*Serum Pregnancy at Screen for 
females only 
Routine Urinalysis 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Pregnancy Testing  
Urine pregnancy testing for females only 
 
6.12.5 Pharmacokinetics 
Approximately 2 mL of blood will be collected for PK analysis at Week 0 (Day 1) [per Day 
8/Visit 4 of Study BBI-4000-CL-105], Week 4 (Day 28 [±3 days]) and Week 24 (Day 168 
[±5 days]). Samples will be collected ≥12 hours from the time of dosing with study drug. 
Details regarding collection, processing, shipping and storage of PK samples will be 
provided in the laboratory reference manual. 
6.13 Concomitant Medications 
6.13.1 General 
Use of chronic medications or as-needed medications (e.g., acetaminophen, topical anesthetic 
[EMLA]) will be permitted during the screening and active study period (unless otherwise 


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restricted, refer to Section 6.13.2), and should be recorded in the source document and on the 
eCRF. Any changes in concomitant medication usage will be recorded in the source 
documents and on the eCRF. If the reason for change is related to an AE, the event should be 
recorded in the source documents and as an AE in the eCRF.  
6.13.2 Concomitant Medication Restrictions 
The following medications will not be permitted during the study period: 
• 
Botulinum toxin to the axillary area  
• 
Newly prescribed anti-anxiety, anti-depressant, and/or psychostimulants (e.g., 
amphetamine) or drugs with known anticholinergic side effects 
• 
Any cholinergic drug (e.g., bethanechol) 
• 
Newly prescribed serotonergic agonist (or drugs that increase serotonin activity 
including SSRIs), betablocker, alpha-adrenergic agonist (clonidine), dopamine partial 
agonist or tricyclic antidepressant treatment 
• 
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., intravenous, oral, inhaled, topical, etc.) 
• 
Any topical prescription treatment for hyperhidrosis  
• 
Any oral or topical homeopathic or herbal treatment (i.e., alternative therapies such as 
sage tablets, chamomile, valerian root and St. John’s Wort) 
• 
Use of potent inhibitors of cytochrome P450 CYP3A (including grapefruit juice) & 
CYP2D6 and transporter inhibitor (OCT2/MATE1/MATE2). Use of topical antifungal 
medications is permitted if not applied in the treatment area. 
6.14 Prevention of Pregnancy during the Study 
6.14.1 Instructions for Female Subjects  
Females must agree to pregnancy testing and use a medically acceptable method of 
contraception while receiving study drug. Acceptable contraceptive methods include the 
following:  
• 
Abstinence for the duration of the study or where partner is sterile (e.g., vasectomy) is 
acceptable form of contraception; 
• 
Hormonal contraception, including oral, injectable, or implantable methods started ≥2 
months prior to screening; OR 
• 
Two forms of non-hormonal contraception, including IUD (≥1-week status post 
placement) and properly used barrier methods (e.g., male or female condoms, cervical 
cap/diaphragm, spermicidal agents). 
6.15 Lifestyle Guidelines 
Not applicable 


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7 
STUDY VISITS 
The procedures and assessments to be performed at each visit are indicated in the 
SCHEDULE OF ACTIVITIES. The timing of each visit (while on treatment) is relative to 
Screening/Enrollment (Week 0 [Day 1]) when enrollment occurs. An estimated time for the 
conduct of each visit is provided as a guide only to the study site personnel and study subject 
(guardian/caregiver) for planning purposes. Note: it will not be considered a departure from 
the protocol if the visit length is shorter or longer than anticipated.  
7.1 
Screening/Enrollment (Week 0 [Day 1]) 
The final visit (Day 8/Visit 4) of Study BBI-4000-CL-105 and Screening/Enrollment (Week 
0 [Day 1]) of this long-term extension Study BBI-4000-CL-108 will take place 
simultaneously. Therefore, procedures required under Study BBI-4000-CL-105, which are 
also required under the extension study will be recorded. The length of the additional time to 
complete additional activities associated with Screening/Enrollment visit is approximately 
1.5 hours.  
• 
Informed Consent Process 
o The parent(s)/legal guardian (s) must provide written informed consent prior 
to any study procedure being done; and 
o If able, the subject must provide assent to participate in the study. 
• 
Interview 
o Evaluate Inclusion/Exclusion criteria\ 
• 
Assessments 
o Obtain and record vital signs 
o Record local tolerability assessment 
• 
Sample Collection 
o Collect blood samples for safety laboratory testing (hematology and 
chemistry), and pregnancy testing (as applicable)  
o Collect urine sample for urine laboratory testing, routine urinalysis and 
pregnancy testing (females only) 
• 
Instructions 
o Inform parent/guardian (caregiver) and subject that dosing will occur in the 
evening at approximately the same time before bedtime.  
o One pump container of sofpironium bromide gel, 15%, enough for 1 month of 
dosing, and one dosing diary card will be dispensed.  
o Review instructions for study drug application and use of the dosing diary 
card. 
o Study site personnel will prime the sofpironium bromide gel, 15% pump 
container with five (5) sequential actuations. 
o Weigh the sofpironium bromide gel, 15% primed pump container with cap.  


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o Provide study product application instruction brochure to subject 
(parent/guardian). 
o Provide gloves if study drug to be dispensed by a parent/guardian. 
o The next visit will be scheduled. 
7.2 
Treatment: Week 4 (Day 28 [±3 days]) through Week 24 (Day 168 [±5 days]) 
Visits will occur at Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [± 5 days]), Week 12 (Day 
84 [±5 days]), Week 16 (Day 112 [±5 days]) and Week 20 (Day 140 [±5 days]). It is 
estimated that each visit will take approximately 1.5 hours. 
• 
Interview 
o Update medications since last visit 
o Assessment of AEs 
• 
Assessments  
o Obtain and record vital signs 
o Perform an abbreviated physical examination 
o Complete an ECG at Week 4 (Day 28 [±3 days]) 
o HDSM-Ax (or HDSM-Ax, Child) and PGI-S assessment (completed by the 
subject) 
o Application site (axillae) tolerability assessment (completed by subject prior 
to Investigator assessment, and Investigator assessment) 
• 
Review dosing diary card (compliance check) at each visit.  
• 
Sample Collection 
o Collect blood sample for safety laboratory testing and PK and urine sample 
for urine laboratory testing at Week 4 (Day 28 [±3 days]); 
o Collect urine sample for pregnancy testing (as applicable) at all visits 
• 
Instructions 
o Collect subject’s previously dispensed sofpironium bromide gel, 15%, pump 
container from prior visit. Record weight of container with cap.  
o Collect subject’s completed dosing diary card from prior visit and review for 
compliance. 
o Prime and weigh to-be-dispensed sofpironium bromide gel, 15% pump 
container with cap prior to dispensing. 
o Dispense one sofpironium bromide gel, 15%, pump container and one dosing 
diary card. 
o Provide gloves if study drug to be dispensed by a guardian (caregiver). 
o Remind subject to return sofpironium bromide gel, 15% pump container and 
dosing diary card for the next study visit. 
o The next visit will be scheduled. 


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7.3 
End of Treatment/Early Termination: Week 24 (Day 168 [±5 days]) 
It is estimated that each visit will take approximately 1.5 hours. 
• 
Interview 
o Update medications since last visit 
o Assessment of AEs 
• 
Assessments  
o Obtain and record vital signs 
o Perform an abbreviated physical examination 
o Complete an ECG 
o HDSM-Ax (or HDSM-Ax, Child) and PGI-S assessment (completed by the 
subject) 
o PGI-C assessed 
o Application site (axillae) tolerability assessment (completed by subject prior 
to Investigator assessment, and Investigator assessment) 
• 
Review dosing diary card (compliance check) 
• 
Sample Collection 
o Collect blood sample for safety laboratory testing and PK and urine sample 
for urine laboratory testing  
o Collect urine sample for pregnancy testing 
• 
Instructions 
o Collect subject’s previously dispensed sofpironium bromide gel, 15%, pump 
container from prior visit. Record weight of container with cap.  
o Collect subject’s completed dosing diary card from prior visit and review for 
compliance. 
o The next visit will be scheduled. 
7.4 
 End of Study: Week 26 (Day 182 [±5 days]) 
The end of study visit will occur at Week 26, approximately 2 weeks after the last application 
of study drug. It is estimated that this visit will take approximately 1.5 hours to complete. 
• 
Interview 
o Update medications since last visit 
o Assessment of AEs 
• 
Assessments  
o Perform an abbreviated physical examination 
o Obtain and record vital signs 


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o Complete an ECG if clinically significant abnormalities noted at Week 24 
(Day 168 [±5 days])  
• 
Sample Collection  
o Collect blood samples for safety laboratory testing and urine sample for urine 
laboratory testing if clinically significant abnormalities noted at Week 24 
(Day 168 [±5 days])  
7.5 
Unscheduled Additional Visit(s)  
An unscheduled visit may occur between visits to evaluate AEs, as applicable. An additional 
unscheduled visit will be scheduled every 7 to 14 days in order to follow-up on unresolved 
AEs or laboratory abnormalities that were still present at the final Visit 8 (Week 26).  
8 
INVESTIGATIONAL PRODUCT 
8.1 
Formulation, Packaging and Labelling  
8.1.1 Formulation 
Sofpironium bromide gel is a clear to slightly translucent, colorless, anhydrous gel 
formulation containing the drug substance in a gel base comprising hydroxypropyl cellulose 
National Formulary (NF), hexylene glycol NF, isopropyl myristate NF, citric acid anhydrous 
United States Pharmacopeia (USP), and alcohol dehydrated USP.  
8.1.2 Packaging and Labeling 
Study drug is packaged in a white colored, metered pump container. One pump container is 
packaged in a carton with 2 applicators. The total gel volume in each pump container is 
approximately 50 mL (~43 g). The gross weight of each full container at baseline is 
approximately 78 to 84 grams. One full pump actuation delivers ~0.67 mL of the gel 
formulation. Therefore, each pump container is sufficient for 30 days of dosing per protocol 
instructions. The external carton will be labeled with “Caution: New Drug – Limited by 
Federal Law to Investigational Use”. 
8.2 
Storage  
When stored in the clinic, the study drug 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. 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. 
When study drug is stored in the subject’s home, it should be kept out of the reach of 
children except when used under supervision by the guardian/caregiver. The study drug 
contains alcohol and is flammable. The subject/caregiver should not store the product near 
open flames or in an area exposed to extreme heat. 
8.3 
Dispensing  
One pump container is packaged in a carton with 2 applicators and will be dispensed at Week 
0 (Day 1), Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [±5 days]), Week 12 (Day 84 [±5 


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days]), Week 16 (Day 112 [±5 days]), and Week 20 (Day 140 [±5 days]). Gloves will be 
provided if study drug to be dispensed by a guardian (caregiver). 
8.4 
 Dosing 
The subject and parent(s)/guardian(s) will be reminded of the proper application of the study 
drug and that the drug will be applied before bedtime (Refer to Appendix C). 
8.5 
Compliance 
The subject and/or the parent(s)/guardian(s) will record that the study drug was applied to 
each axilla (right and left) and when the subject applied the study drug in the dosing diary 
card. The site personnel will review the dosing diary card and weigh the pump container with 
cap on, at Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [±5 days]), Week 12 (Day 84 [±5 
days]), Week 16 (Day 112 [±5 days]), Week 20 (Day 140 [±5 days]), and Week 24 (Day 168 
[±5 days]). 
8.6 
Study Drug Accountability 
Inventory records must be readily available for inspection by the study monitor and/or 
auditor, and open to inspection by regulatory authorities at any time. Study drug will be 
received and dispensed by the designated study staff. All study drug will be accounted for on 
the study drug inventory/accountability log and will include: 
• 
Subject ID  
• 
Date/time dispensed 
• 
Amount dispensed  
• 
Amount remaining in inventory 
Damaged or lost study drug will also be accounted for and recorded in the drug 
accountability records. 
At completion of the study, the Investigator (or designee) is responsible for returning all 
unused study drug and used study drug containers to the Sponsor (or designee) and must 
verify that no supplies remain in the investigator’s possession. 
8.7 
 Blinding 
Not applicable as this is an open-label study.  
8.8 
 Breaking the Study Blind 
Not applicable 
9 
PROTOCOL VIOLATIONS 
A protocol violation occurs when the study subject, Investigator, or Sponsor fails to adhere to 
significant protocol requirements affecting the inclusion, exclusion, study subject safety and 
primary endpoint criteria. Protocol violations for this study include, but are not limited to, the 
following: 
• 
Failure to meet inclusion/exclusion criteria 
• 
Dosing error 


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• 
Out of window blood sample collection or visit 
Failure to comply with GCP guidelines will also result in a protocol violation. The Sponsor 
will determine if a protocol violation will result in withdrawal of a study subject or if data 
analysis will be censored. 
When a protocol violation occurs, it will be discussed with the Investigator, and the details 
will be documented and reviewed by the Sponsor representative and the Investigator. A copy 
of such documentation will be filed in the site’s regulatory binder and in the Sponsor’s files 
and may be reported to the IRB/IEC as applicable. 
10 ADVERSE EVENTS 
10.1 Safety Evaluations 
The Investigator is responsible for the appropriate medical care and the safety of subjects 
who have entered this study. Safety will be assessed by physical examinations, laboratory 
tests, and measurement of vital signs assessed as indicated throughout the study schedule. 
Clinically significant changes in these parameters may be captured as AEs. 
The Investigator must document any AE experienced by subjects who have entered this study 
and report all SAEs to the Sponsor (see Section 10.3.1). Contact information for the 
Sponsor’s medical monitor is provided on the protocol covering page. 
10.2 Adverse Events 
10.2.1 Definition of Adverse Events 
According to the Code of Federal Regulations, 21 CFR Parts 312.32 and 320.32 (IND Safety 
Reporting, Applicability of requirements regarding an "Investigational New Drug 
Application"), FDA Guidance for Industry (Investigational New Drug Safety Reporting 
Requirements for Human Drug and Biological Products and Safety Reporting Requirements 
for Bioavailability and Bioequivalence Studies in Humans) (Federal Register/Vol. 75, No. 
188/September 29, 2010) and ICH E2A (Clinical Safety and Data Management: Definitions 
and Standards for Expedited Reporting): 
• 
An AE means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
• 
A suspected drug-related adverse reaction means any AE for which there is a 
reasonable possibility that the drug caused the AE. 
The following information should be considered when determining whether to classify a test 
result, medical condition, or other incident as an AE: 
• 
Adverse events will be recorded from the time of informed consent. 
• 
Abnormal laboratory values should not generally be recorded as an AE unless an 
intervention is required, the laboratory abnormality is associated with clinical signs or 
symptoms, or the lab abnormality results in study termination or 
interruption/discontinuation of study treatment. When recording an AE resulting from 
a laboratory abnormality, the resulting medical condition rather than the abnormality 
itself should be recorded (e.g., record “anemia” rather than “low hemoglobin”). 


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• 
Complications that occur in association with a protocol-mandated intervention (e.g., 
invasive procedures such as biopsies) should be recorded as AEs. 
• 
Whenever possible, the Investigator should group signs or symptoms that constitute a 
single diagnosis under a single event term. For example, cough, rhinitis, and sneezing 
might be grouped together as “upper respiratory tract infection”. If possible, abnormal 
laboratory results that meet the definition of an AE (see above) should be reported as a 
clinical diagnosis rather than the abnormal value itself (e.g., “anemia” rather than 
“decreased blood count”). 
10.2.2 Documentation and Monitoring Adverse Events 
All AEs encountered during the clinical trial following subject consent through the last study 
visit will be recorded on the appropriate Adverse Events case report form (eCRF). 
Special considerations: 
• 
Elective procedures or routinely scheduled treatments are not considered AEs. 
However, an untoward medical event occurring in association with a prescheduled 
elective procedure should be recorded as an AE. 
• 
A baseline condition is not considered an AE unless the condition worsens following 
study drug administration. 
• 
Death itself is not considered an AE; it is, instead, the outcome of an AE. 
• 
SAEs that are considered related (i.e., determined to be possibly, probably, or 
definitely related) to sofpironium bromide by the Investigator or Sponsor should be 
followed until the event resolves or stabilizes (see Section 10.3.1). 
10.2.3 Assessment of Adverse Events 
For each reported AE, the start and resolution dates, intensity, seriousness (i.e., whether the 
event meets the definition of an SAE [Section 10.3.1]), relationship of the event to the study 
drug, action taken regarding study drug, and outcome of the event will be documented on the 
eCRF. 
Intensity 
The following definitions should be used to assess and grade AE intensity, including 
laboratory abnormalities judged to be clinically significant. 
 
Severity 
Grade 
Description 
Mild  
1 
Awareness of sign or symptom, but easily tolerated 
Moderate  
2 
Discomfort enough to cause interference with usual activity 
Severe 
3 
Incapacitating with inability to work or do usual activity 
Note: a severe AE is not necessarily serious. 
Relationship  
The relationship of a reported AE to study drug should be assessed using the guidelines 
presented in the following table.  
 


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Degree of Certainty 
Description 
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. 
 
Outcome 
Each AE will be characterized according to the outcomes described in the following table. 
 
Outcome 
Description 
Recovered/Resolved 
The subject has fully recovered from the event with no 
observable residual effects. 
Recovering/Resolving 
The effects of the event are improving, or events have 
stabilized (are constant and not expected to improve or 
worsen) but have not returned to baseline. 
Not recovered/Not Resolved 
The effects of the event are still present and changing. The 
event is not considered stabilized or resolved. 
Recovered/Resolved with Sequelae 
The subject has fully recovered from the event with some 
observable residual effects. 
Fatal 
The event was the primary cause of death (may or may not 
be the immediate cause of death). 
Unknown 
The event outcome is unknown. 
Death is an outcome of an event and not an event per se. Sudden death or death due to 
unexplainable cause(s) is to be reported, but follow-up will be pursued until cause of death is 
determined. 
Action Taken with Study Drug 
Action taken with study drug in relation to each AE will be characterized as follows: 
• 
None 
• 
Drug withdrawn  
• 
Drug interrupted  
• 
Unknown 
• 
Not applicable 


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• 
Other (specify on eCRF) 
10.3 Serious Adverse Events 
Any AE that is serious (see definition below) and occurs after administration of study drug 
must be reported to the Sponsor within 24 hours of discovery of the event. An event 
occurring after informed consent but before administration of study drug that is considered 
serious and possibly related to a protocol procedure must also be reported to the Sponsor 
within 24 hours of discovery of the event. 
10.3.1 Definition and Reporting Procedures 
An AE should be classified as an SAE if it meets one of the following criteria. 
 
Fatal: 
The AE resulted in death. 
Life Threatening: 
The AE placed the patient at immediate risk of death. This classification 
does not apply to an AE that hypothetically might cause death if it were 
more severe. 
Hospitalization: 
The AE required or prolonged an existing inpatient hospitalization. 
Hospitalizations for elective medical or surgical procedures or treatments 
planned before the signing of informed consent in the study or routine 
check-ups are not serious AEs by this criterion. Hospitalizations or 
prolonged hospitalizations for scheduled therapy need not be captured as 
SAEs. 
Disabling/Incapacitating: 
Resulted in a substantial and permanent disruption of the patient’s ability 
to carry out activities of daily living. 
Congenital Anomaly or Birth 
Defect: 
An adverse outcome in a child or fetus of a patient exposed to the study 
drug or study treatment regimen before conception or during pregnancy. 
Medically Significant: 
The AE did not meet any of the above criteria but could have jeopardized 
the patient and might have required medical or surgical intervention to 
prevent one of the outcomes listed above. 
Every SAE (regardless of suspected causality) should be reported to the Sponsor within 24 
hours of discovery of the event. The processes for reporting and documenting SAEs are 
provided in the study manual. Investigators are responsible for reporting these events to their 
IRB/IEC in accordance with federal and institutional laws and regulations. 
Additional updates from the Investigator may be necessary as more information becomes 
available on the SAE, and all treatment-related SAEs will be followed until the acute event 
has resolved or stabilized, even if the subject discontinues study participation prior to the 
SAE resolution. Any new information or follow-up information pertaining to previously 
reported SAEs will be reported to the Sponsor within 24 hours of becoming aware of the new 
or follow-up information. The new or follow-up information should be faxed to the Sponsor 
at 1-866-666-7392 or emailed to safety@brickellbio.com. 
Any SAE that occurs after study completion and is considered by the Investigator to be 
related to sofpironium bromide, should be reported to the Sponsor. 
10.3.2 Reporting Serious Adverse Events to Regulatory Agencies 
The Sponsor will determine which SAEs qualify for expedited reporting to regulatory 
agencies. SAEs that qualify for expedited reporting will be submitted to regulatory agencies 
in accordance with applicable federal regulations.  


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10.4 Follow-up of Adverse Events and Laboratory Test Abnormalities 
Adverse event information will be collected during the clinical trial from the time the subject 
signs informed consent through the final study visit. SAEs that are considered related to 
study drug by the Investigator or Sponsor should be followed until the events resolve or 
stabilize. 
10.5  Pregnancy Reporting 
10.5.1 Definition of Female of Childbearing Potential 
For purposes of this study, all female subjects are considered of childbearing potential. 
10.5.2 Testing and Acceptable Methods of Birth Control 
Females must agree to periodic pregnancy testing and use a medically acceptable method of 
contraception while receiving protocol-assigned study drug. Refer to Section 6.14.1 for 
additional information. 
10.5.3 Time Period for Collecting Pregnancy Information 
Females of child bearing potential 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. 
10.5.4 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 investigational product 
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 to 1-866-666-7392 or email at safety@brickellbio.com. 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. 


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11 DATA ANALYSIS AND STATISTICAL METHODS 
11.1 Sample Size Determination  
A sample size of twenty-four (24) subjects is based on the maximum planned enrollment 
under Study BBI-4000-CL-105.  
11.2 Analysis Populations 
Two populations will be used for analysis: Safety and PK. The definition of these two 
populations follows:  
• 
Safety Population: All enrolled subjects who applied at least one dose of study drug 
and have at least one post-baseline safety assessment. 
• 
Pharmacokinetic Population: All enrolled subjects who applied at least one dose of 
study drug and have at least one quantifiable PK sample for analysis. 
11.3  Statistical Analysis 
11.3.1 General Statistical Methodology 
• 
Baseline is defined as the last assessment prior to the first application of study drug on 
Day 1 under Study BBI-4000-CL-105. 
• 
All statistical processing will be performed using Statistical Analysis System (SAS®) 
unless otherwise stated. 
• 
Continuous data will be summarized using descriptive statistics (number of values, 
mean, standard deviation, median, minimum and maximum). Categorical data will be 
summarized using frequency tables (frequencies and percent). 
• 
A SAP, describing all statistical analyses will be provided as a separate document. The 
SAP will be finalized prior to locking the database. The SAP will contain any 
modifications to the analysis plan presented below. 
11.3.2 Demographics, Baseline Characteristics, Medical History, Hyperhidrosis 
History, and Concomitant Medications 
Demographic data, baseline characteristics, medical history including history of axillary 
hyperhidrosis, and prior and concomitant medications will be summarized using descriptive 
statistics.  
11.3.3 Treatment Compliance 
The subject or parent(s)/guardian(s) will record the date and time of all applications made to 
the right and left axilla or missed applications in the dosing diary card. Subject compliance 
during the overall treatment period and by visit will be summarized. 
11.3.4 Drug Exposure 
Amount of study drug (weight) and the number of days of study drug application will be 
summarized. 


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11.4  Primary Analysis 
11.4.1 Safety 
Safety evaluations will consist of AEs, local application site tolerability, vital signs, 
laboratory measurements (hematology, chemistry, and urinalysis, and pregnancy testing), 
ECGs and physical examinations. Full details will be specified in the SAP. A general 
description of the planned analysis is as follows:  
• 
Adverse Events: 
o Adverse events will be descriptions will be mapped to standard terms, i.e., 
MedDRA System Organ Class and Preferred Term. 
o Adverse events that occurred during the screening period will be listed 
separately and will not be included in the AE tabulations. 
o Adverse events that start on or after first dose will be considered a TEAE. At 
each post-baseline visit, the number and proportion of subjects reporting any 
given TEAE will be tabulated by severity; each subject will be counted only 
once according to the worst severity reported up to the current visit. Separate 
tables will be constructed for (a) all reported TEAEs, (b) protocol treatment 
related TEAEs, (c) serious TEAEs, and (d) TEAEs leading to protocol 
treatment discontinuation. 
• 
At each visit, local tolerability (burning, itching, stinging, scaling, and erythema at 
either axilla) will be described by severity as defined in Appendix F.  
• 
Vital signs will be summarized similarly as for laboratory parameters but without shift 
tables. 
• 
Laboratory parameters will be descriptively summarized (mean, SD, median, 
minimum, maximum) for values at each visit and for changes from baseline at each 
subsequent visit. In addition, at each post baseline visit, parameter status (low, normal, 
high) will also be summarized as shift tables vs. baseline status.  
• 
Descriptive statistics and/or frequency tables will be prepared as appropriate for 
physical examinations, and ECG (HR, RR, QTcF, PR, and QRS) parameters 
• 
Concomitant medications will be mapped according to the World Health Organization 
Drug Dictionary and will be presented in data listings. 
11.4.2 Pharmacokinetics 
Plasma concentrations of sofpironium and BBI-4010, will be determined using validated 
liquid chromatography with tandem mass spectrometry (LC-MS/MS) analytical methods. 
The lower limit of quantification (LLQ) of the assay in plasma is 0.0555 ng/mL for both 
sofpironium and BBI-4010. Specifics of the analytical procedures will be provided in 
separate bioanalytical documentation. 
Individual plasma Ctrough values of sofpironium and BBI-4010 will be summarized 
descriptively using the arithmetic mean, SD, CV (%), median, minimum and maximum. 
Mean (±SD) Ctrough values will also be presented graphically by week to assess exposure, 
accumulation and steady state 
Additional details regarding PK analysis will be provided in the SAP. 


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11.5 Exploratory Analysis 
• 
Descriptive summaries will be provided for HDSM-Ax and HDSM-Ax, Child, 
Summary Questions (No. 4 and No. 5) and PGI-S. Mean changes from baseline and 
observed values will be summarized by time point. The SAP will contain full details. 
• 
For HDSM-Ax and HDSM-Ax, Child, the mean of the items in Section No. 1, No. 2, 
and No. 3 will be calculated for every subject at each time point. The mean will be 
derived by taking the total score and dividing it by the number of questions answered. 
Subjects must answer ≥6 of the 11 sub-items to be evaluable for HDSM-Ax or 
HDSM-Ax, Child total score. Observed values and changes from baseline at each time 
point will be summarized and plotted over time using descriptive statistics. 
• 
For the HDSM-Ax or HDSM-Ax, Child Summary Questions (No. 4 and No. 5), the 
score for each question, will be reported for every subject at every visit and 
summarized and plotted over time using descriptive statistics.  
• 
For PGI-S, the score will be reported for every subject at every visit and summarized 
and plotted over time using descriptive statistics. 
• 
For PGI-C, the score will be reported for every subject at Week 12 and Week 24 
(EOT) and summarized and plotted over time using descriptive statistics. 
Missing data will not be imputed for any analyses.  
11.6 Interim  
No interim analyses are planned. 
12 DATA COLLECTION, RETENTION AND MONITORING 
12.1 Data Collection Instruments 
The Investigator will maintain adequate and accurate source documents designed to record 
all observations and other pertinent data for each study subject treated with the test article. 
Study personnel at each site will enter data from source documents corresponding to a study 
subject’s visit into the protocol-specific electronic Case Report Form (eCRF) when the 
information corresponding to that visit is available.  
Study subjects will not be identified by name in the study database or on any study 
documents to be collected by the Sponsor (or designee) but will be identified by a site 
number and study subject number.  
When changes or corrections are made in the eCRF, the EDC systems 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 is responsible for all information collected on study subjects enrolled in this 
study. All data collected during the course of this study must be reviewed and verified for 
completeness and accuracy by the Investigator. Copies of final completed eCRFs will be 
provided on a compact disk or other similar media for archiving at the study site following 
database lock and at or prior to study closure. 


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12.2 Data Management Procedures 
The data will be entered into a validated database. The Data Management group will be 
responsible for data processing, in accordance with procedural documentation. Database lock 
will occur once quality assurance procedures have been completed. All procedures for the 
handling and analysis of data will be conducted using good computing practices meeting 
FDA guidelines for the handling and analysis of data for clinical trials. 
12.2.1 Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data 
validation checks will be implemented and applied to the database on a regular basis. Queries 
are entered, tracked, and resolved through the EDC system directly. The study database will 
be updated in accordance with the resolved queries. All changes to the study database will be 
documented. 
12.2.2 Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel 
must log into the system using their secure user name and password in order to enter, review, 
or correct study data. These procedures must comply with Title 21 of the Code of Federal 
Regulations (21 CFR Part 11) and other appropriate international regulations. All passwords 
will be strictly confidential. Data should be entered onto the eCRF approximately no later 
than 72 hours after the visit has taken place. 
12.2.3 Medical Information Coding 
For medical information, the following thesauri will be used: 
• 
Latest version of the MedDRA for medical history and AEs; and 
• 
World Health Organization Drug Dictionary for prior and concomitant medications. 
12.2.4 Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the uploaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, 
will be referred to the investigative site for resolution through data queries. The eCRFs must 
be reviewed and electronically signed by the Investigator who signed the protocol. 
12.3 Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be maintained. 
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database. At critical junctures of the protocol (e.g., production of interim 
reports and final reports), data for analysis is locked and cleaned per established procedures.  
12.4 Availability and Retention of Investigational Records 
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), IRB/IEC, and Regulatory Agency (e.g., FDA) 
inspectors upon request. A file for each study subject must be maintained that includes the 


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signed Informed Consent, HIPAA Authorization and Assent Form and copies of all source 
documentation related to that study subject. The Investigator must ensure the reliability and 
availability of source documents from which the information on the eCRF was derived. 
All study documents (patient and subject files, signed informed consent forms, copies of 
eCRFs, Study File Notebook, etc.) must be kept secured for a period of two years following 
marketing of the investigational product or for two years after centers have been notified that 
the IND has been discontinued. There may be other circumstances for which the Sponsor is 
required to maintain study records and, therefore, the Sponsor should be contacted prior to 
removing study records for any reason. 
12.5 Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor (or designee) 
according to the U.S. CFR Title 21 Parts 50, 56, and 312 and ICH Guidelines for GCP (E6 
(R2)). By signing this protocol, the Investigator grants permission to the Sponsor (or 
designee), and appropriate regulatory authorities to conduct on-site monitoring and/or 
auditing of all appropriate study documentation. 
12.6 Subject Confidentiality 
In order to maintain study subject confidentiality, only a site number, and subject number 
will identify all study subjects on eCRFs, blood samples, and other documentation submitted 
to the Sponsor. Additional study subject confidentiality issues (if applicable) are covered in 
the Clinical Study Agreement. 
12.7 Retained Blood Samples 
Blood samples collected during the study for pharmacokinetic analysis may be retained for 
future testing as necessary. Study subject’s confidentiality will be maintained and only the 
site and study subject number will identify the sample. No other linked or identifying 
information is maintained by the Sponsor.  
13 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
The study will be conducted according to the Declaration of Helsinki, Protection of Human 
Subjects (21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical 
Investigators (21 CFR 312 Subpart D). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number only. All study records will be kept in a locked 
secured area. The Investigator must also comply with all applicable privacy regulations (e.g., 
Health Insurance Portability and Accountability Act of 1996, EU Data Protection Directive 
95/46/EC). 
13.1 Protocol Amendments 
Any amendment to the protocol will be written by the Sponsor or Sponsor designee. Protocol 
amendments cannot be implemented without prior written IRB/IEC approval except as 
necessary to eliminate immediate safety hazards to study subjects/patients. A protocol 
amendment intended to eliminate an apparent immediate hazard to study subjects/patients 
may be implemented immediately, provided the IRBs are notified within five working days. 


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13.2 Institutional Review Boards and Independent Ethics Committees 
The protocol and consent forms [parental consent and assent collectively referred to as 
“consent”] will be reviewed and approved by the IRB/IEC of each participating center prior 
to study initiation. Serious adverse experiences regardless of causality will be reported to the 
IRB/IEC in accordance with the standard operating procedures and policies of the IRB/IEC, 
and the Investigator will keep the IRB/IEC informed as to the progress of the study. The 
Investigator will obtain assurance of IRB/IEC compliance with regulations. 
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, consent forms, information concerning 
subject/patient recruitment, payment or compensation procedures, or other pertinent 
information) will be submitted to the IRB/IEC. The IRB/IECs written unconditional approval 
of the study protocol and the informed consent form will be in the possession of the 
Investigator before the study is initiated. The IRB/IECs unconditional approval statement 
will be transmitted by the Investigator to the Sponsor prior to the shipment of study supplies 
to the site. This approval must refer to the study by exact protocol title and number and 
should identify the documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without prior 
written IRB/IEC approval except when necessary to eliminate immediate hazards to the 
subject or when the change(s) involves only logistical or administrative aspects of the study. 
Such modifications will be submitted to the IRB/IEC and written verification that the 
modification was submitted and subsequently approved should be obtained.  
The IRB/IEC must be informed of revisions to other documents originally submitted for 
review; serious and/or unexpected adverse experiences occurring during the study in 
accordance with the standard operating procedures and policies of the IRB; new information 
that may affect adversely the safety of the subjects/patients of the conduct of the study; an 
annual update and/or request for re-approval; and when the study has been completed. 
13.3 Informed Consent Form – General Provisions 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, 
US Code of Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 
50.27, and CFR Part 56, Subpart A), the Health Insurance Portability and Accountability Act 
(HIPAA, if applicable), and local regulations. Also refer to Protocol Section 6.1. 
The Investigator will prepare the informed consent form, assent and HIPAA authorization 
and provide the documents to the Sponsor or designee for approval prior to submission to the 
IRB/IEC. The consent/assent forms generated by the Investigator must be acceptable to the 
Sponsor and be approved by the IRB/IEC. The written consent document will embody the 
elements of informed consent as described in the International Council on Harmonisation and 
will also comply with local regulations. The Investigator will send an IRB/IEC-approved 
copy of the Informed Consent Form and Assent Form to the Sponsor (or designee) for the 
study file. 
A properly executed, written, informed consent will be obtained from each study subject or 
the subject’s legally authorized representative prior to entering the study subject into the trial 
and conducting any Screening visits. Information should be given in both oral and written 
form and study subjects (or their legally authorized representatives) must be given ample 
opportunity to inquire about details of the study. If appropriate and required by the local 


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IRB/IEC, assent from the study subject will also be obtained. If a study subject is unable to 
sign the ICF and the HIPAA authorization, a legal representative may sign for the study 
subject. A copy of the ICF (and assent) will be given to the study subject or legal 
representative of the study subject and the original will be maintained with the study 
subject’s records. 
13.4 Publications  
Brickell Biotech, Inc. as the Sponsor has proprietary interest in this study. Authorship and 
manuscript composition will reflect joint cooperation between the Investigator and Brickell 
Biotech, Inc. 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, Inc. 
13.5 Clinical Trials Registration 
If the study falls within the requirements of an “applicable clinical trial" (ACT) as defined in 
section 402(j) of the Public Health Service Act, the study will be registered by the Sponsor 
(or designee) on ClinicalTrials.gov. The name of the Investigator or investigational site may 
be included under Contacts and Locations, as required. 
14 SPONSOR DISCONTINUATION CRITERIA 
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of the Sponsor. 
In addition, the Sponsor retains the right to discontinue development of the referenced 
investigational drug at any time. 
If the study is prematurely terminated or discontinued, the Sponsor, or designee, will 
promptly notify the Investigator. After notification, the Investigator must contact all 
participating study subjects within 5 business days. As directed by the Sponsor all study 
materials must be collected and all eCRFs completed to the greatest extent possible. 
 


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15 REFERENCES 
Howie SRC. Blood sample volumes in child health research: review of safe limits. Bull 
World Health Organ.2011;89:46–53.  
Kirsch BM, Burke L, Hobart J, et al. The hyperhidrosis disease severity measure axillary: 
conceptualization and development of item content. J Drugs Dermatol. 
2018;17(7):707-714. 


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APPENDIX A  
HDSM-AX, CHILD (≥9 TO <12 YEARS OF AGE)  


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APPENDIX B  
HDSM-AX (≥12 YEARS OF AGE) 


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APPENDIX C  
STUDY DRUG APPLICATION AND SUBJECT INSTRUCTIONS 
AND DOSING DIARY CARD 
• The study drug will be applied every day, at home before bed, at about the same time.  
• The study drug will be applied as follows: 
 Steps 
 Expose the underarm areas and ensure they are dry. Do not wash the underarm areas 
for at least 30 minutes prior to application. 
 If caregiver will be applying the gel, gloves (provided) should be worn while 
dispensing the gel and when washing applicator. 
 Hold the plastic applicator between the index and middle fingers and the thumb of the 
left hand. Carefully, by applying consistent pressure to the actuator with an index 
finger, dispense the gel of ONE FULL actuation onto the dome of the white plastic 
applicator. 
 Immediately apply study drug to the right underarm area. 
 Distribute all the gel expressed using the plastic applicator in a way that covers all the 
underarm area by gently applying a layer of the product. 
 Repeat steps 3, 4 and 5 for the left underarm. If self-applying use the right hand. 
 Wash both hands and the plastic applicator thoroughly for about 2 minutes. 
 Allow the study drug to dry for 5 minutes before putting any clothes on the upper 
body. 
 Record in the dosing diary card each time (date and time) the study drug is applied 
and check off that it was applied to the right and left underarm. 


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Important information: 
• 
Avoid touching the underarm. 
• 
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 in the morning then it 
should be at least 30 minutes before study product application. Ensure the underarm areas 
are dry prior to application of the study product. 
• 
Subjects should not apply any other product to the axillary area (including deodorant) for 
at least 8 hours after study product application.  
• 
The subject/caregiver should use the applicator provided to avoid contact with skin of the 
hands. Gloves will be provided and should be worn if gel applied by the caregiver. 
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. 
• 
The study product contains alcohol and is flammable. The subject/caregiver should avoid 
fire, flames or smoking during the application and until the gel has dried. The subject 
should not expose the container to fire, flames or extreme heat. 


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SUBJECT/CAREGIVER 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/your child participates in this study, you/your child will be expected to: 
• 
Follow the instructions that are given and come to the study center for visits with the study doctor 
or study staff or allow a visiting nurse to come to your/your child’s home or school to complete 
the study visit. 
• 
Record in the dosing diary card each time (date and time) the study drug is applied. Check off 
that the study drug was applied to your/your child’s right and left underarm.  
• 
DO NOT apply the study drug before a study visit (or when the study nurse will be visiting). 
• 
Tell the study doctor or study staff about any changes in your/your child’s health or the way 
you/your child are feeling. 
• 
Tell the study doctor or study staff if you/your child want to stop being in the study at any time. 
• 
Do not shower, shave, or wash the underarm area within 30 minutes of study drug application and 
for at least 8 hours after study drug application. 
• 
Be careful not to touch the eyes or mouth with the gel or with your hands while applying the gel. 
• 
You/your child must practice the required method of birth control throughout the entire study if 
you/your child are able to become pregnant. 
• 
You/your child must not breastfeed while you/your child are in the study (for applicable females). 
• 
Use a loose T-shirt or similar clothing item and avoid touching the underarm area. 
• 
Do not start any new medications or change your/your child’s medications without approval from 
the study doctor. 
• 
Do not allow access to the study drug assigned to you/your child to anyone beside the study staff. 
• 
Store the study medications according to the instructions on the label. 
 
IMPORTANT:  
• 
The investigational product contains alcohol and is flammable.  
• 
Avoid fire, flames or smoking during the application and until the gel has dried.  
• 
Do not expose the container to fire, flame or extreme heat. 
 
Bring the previously dispensed Study Drug pump container to every clinic visit along with the 
completed dosing diary card.


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Dosing Diary Card BBI-4000-CL-108 
(EXAMPLE INFORMATION TO BE COMPLETED BY 
SUBJECT/PARENT/GUARDIAN) 
 
 
 
Apply 1 full pump to each axilla before bed. 
Check areas applied and enter time application 
complete  
 
Week 1 
Day 
Date 
(dd/mm) 
 
Year_____ 
Time of 
Dosing 
(PM) 
Right 
Axilla 
 
 
Left  
Axilla 
 
 
Comments 
Parent/ 
Guardian 
Dose 
Verification 
(signature) 
1 
 
 
: 
 
 
 
 
2 
 
 
: 
 
 
 
 
3 
 
 
: 
 
 
 
 
4 
 
 
: 
 
 
 
 
5 
 
 
: 
 
 
 
 
6 
 
 
: 
 
 
 
 
7 
 
 
: 
 
 
 
 
Week 2 
8 
 
 
: 
 
 
 
 
9 
 
 
: 
 
 
 
 
10 
 
 
: 
 
 
 
 
11 
 
 
: 
 
 
 
 
12 
 
 
: 
 
 
 
 
13 
 
 
: 
 
 
 
 
14 
 
 
: 
 
 
 
 
 
Bring the previously dispensed Study Drug pump container to every clinic visit along with the 
completed dosing diary card.


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APPENDIX D  
EXAMPLES OF POTENT INHIBITORS CYP3A AND CYP2D6 
Example Potent Inhibitors of CYP3A 
apigenin 
hydroxyzine 
protease inhibitors 
antipsychotics 
interferon 
ritonavir 
candesartan 
isoniazid 
St. John’s Wort  
(and other herbal 
supplements) 
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 CYP2D6 
bupropion 
fluoxetine 
paroxetine 
quinidine 
terbinafine 
 
 
Also refer to FDA reference link “Drug Development and Drug Interactions: Table of 
Substrates, Inhibitors and Inducers” 
[http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInter
actionsLabeling/ucm093664.htm#table2-2] 
Concomitant medication restrictions (6.13.2) 
 


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APPENDIX E 
EXAMPLES OF POTENT INHIBITORS OF 
OCT-2/MATE1/MATE2 TRANSPORTERS  
Example Potent Inhibitors of OCT2 
Cimetidine 
 
 
 
Example Potent Inhibitors of MATE1/MATE2 
Cimetidine 
Dolutegravir 
Isavuconazole 
Ranolazine 
Trimethoprim 
Vandetanib 
  
Also refer to FDA reference link “Drug Development and Drug Interactions: Table of 
Substrates, Inhibitors and Inducers” 
[http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInter
actionsLabeling/ucm093664.htm#table2-2] 
Prohibited medications (6.13.2) 
 
 


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APPENDIX F  
APPLICATION SITE TOLERABILITY ASSESSMENTS 
These assessments are to be performed for each axilla individually. The designation of 
“Right Axilla” or “Left Axilla” in the source documents and eCRFs 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): As reported by the Subject to the Investigator, the severity of 
any symptoms of burning, stinging or itching at the application-site within the previous 24 
hours and further any such symptoms persisting longer than 1 hour following study drug 
application will be described specifically by severity using the following standardized scales: 
 
Score 
Burning 
Stinging 
Itching 
0 = Absent 
Normal, no discomfort 
Normal, no discomfort 
Normal, no discomfort 
1 = Minimal 
An awareness, but no 
discomfort  
An awareness, but no 
discomfort  
An awareness, but no 
discomfort  
2 = Mild 
Noticeable discomfort 
causing intermittent 
awareness 
Noticeable discomfort 
causing intermittent 
awareness 
Noticeable discomfort 
causing intermittent 
awareness 
3 = Moderate 
Noticeable discomfort 
causing continuous 
awareness 
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 
Definite discomfort causing 
continuous awareness, 
interfering occasionally 
with normal daily activities 
Local tolerability (Investigator): The Investigator will assess the drug-application site for 
the existence of significant local symptoms. Significant local symptoms are defined as those 
not ordinarily observed following application of a topical product. The following 
standardized scales will be used to describe specifically the severity of any erythema or 
scaling:  
 
Score 
Scaling 
Erythema 
0 = Absent 
No scaling 
No redness 
1 = Minimal 
Fine scaling, barely perceptible 
Faint red or pink coloration, barely 
perceptible 
2 = Mild 
Slight scaling, noticeable only with light 
scratching 
Light red or pink coloration 
3 = Moderate 
Definitely noticeable scaling 
Medium red coloration 
4 = Severe 
Extensive scaling 
Beet red coloration 
 

SAP_001.pdf: 
NCT03785587




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TABLE OF CONTENTS 
ABBREVIATIONS ...................................................................................................................4 
1 
REVISION HISTORY ....................................................................................................5 
2 
INTRODUCTION ..........................................................................................................6 
2.1 
Background ................................................................................................................6 
2.2 
Rationale .....................................................................................................................6 
3 
STUDY OUTLINE .........................................................................................................6 
4 
SCHEDULE OF ACTIVITIES .......................................................................................8 
5 
STUDY DURATION ...................................................................................................10 
6 
STUDY POPULATON .................................................................................................10 
7 
STUDY OBJECTIVES AND ENDPOINTS ................................................................10 
7.1 
Objectives .................................................................................................................10 
 
Primary Objectives ..............................................................................................10 
7.1.1.1 
Safety.................................................................................................................10 
7.1.1.2 
Pharmacokinetics ..............................................................................................10 
 
Exploratory Objectives ........................................................................................10 
7.2 
Endpoints ..................................................................................................................11 
 
Primary Endpoints ...............................................................................................11 
7.2.1.1 
Safety.................................................................................................................11 
7.2.1.2 
Pharmacokinetics ..............................................................................................11 
 
Exploratory Endpoints .........................................................................................11 
7.3 
Study Assessments ...................................................................................................11 
 
Safety ...................................................................................................................11 
 
Pharmacokinetics .................................................................................................12 
 
Efficacy ................................................................................................................12 
8 
DOSING AND COMPLIANCE ...................................................................................12 
9 
BREAKING THE BLIND ............................................................................................12 
10 
STUDY REVIEW COMMITTEE ................................................................................12 
11 
SAMPLE SIZE .............................................................................................................13 
12 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS .......................................13 
12.1 
Analysis Populations ................................................................................................13 
12.2 
Interim Analysis .......................................................................................................13 
12.3 
General Considerations for Analysis ........................................................................13 
 
Safety and Efficacy Analysis ...............................................................................13 
 
Pharmacokinetics .................................................................................................14 
 
Handling of PK Concentration Values Below the Limit of Quantification ........14 


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Handling of Missing PK Sampling or Concentration Data .................................14 
 
Handling of PK Outliers ......................................................................................14 
 
Handling of Actual vs. Planned PK Sampling Timepoints .................................15 
 
Handling of Individual PK Data and Summary Data Formats ............................15 
12.4 
Derived and Transformed Data ................................................................................15 
12.5 
Assessment Days and Windows ...............................................................................15 
12.6 
Missing Safety and Efficacy Data ............................................................................16 
12.7 
Medication and Adverse Event Coding Dictionaries ...............................................16 
12.8 
Protocol Deviations and Violations ..........................................................................16 
13 
STATISTICAL ANALYSIS .........................................................................................16 
13.1 
Baseline Parameters, Demographics, Medical History, Hyperhidrosis History, 
Concomitant Medications, Disposition and Drug/Alcohol Screening, and 
Pregnancy Testing ....................................................................................................16 
13.2 
Drug Exposure and Treatment Compliance .............................................................17 
13.3 
Primary Analyses .....................................................................................................18 
 
Safety ...................................................................................................................18 
 
Pharmacokinetics .................................................................................................18 
13.4 
Exploratory Analysis ................................................................................................19 
14 
REFERENCES ..............................................................................................................19 
15 
APPENDICES ..............................................................................................................20 
15.1 
Appendix A: Preliminary Table of Contents for Tables, Listings, Figures for Safety 
and Efficacy ..............................................................................................................20 
15.2 
Appendix B: Preliminary Table of Contents for Tables, Listings, Figures for PK ..24 
15.3 
Appendix C: HDSM-Ax, Child (≥9 to <12 years of age) ........................................25 
15.4 
Appendix D: HDSM-Ax (≥12 years of age) ............................................................28 
15.5 
Appendix E: Application Site Tolerability Assessments .........................................31 
 
 


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ABBREVIATIONS 
Abbreviations 
Definitions 
AE 
Adverse event 
CFR 
Code of Federal Regulations 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
Ctrough 
Trough concentration 
CV 
Coefficient of variation 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EOT 
End of treatment 
EOS 
End of study 
HDSM-Ax 
Hyperhidrosis Disease Severity Measure-Axillary 
HDSM-Ax, Child 
Hyperhidrosis Disease Severity Measure-Axillary, Child 
hr, h, hrs 
Hour(s) 
LC-MS/MS 
Liquid chromatography with tandem mass spectrometry 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram(s) 
min 
Minutes 
mL 
Milliliter(s) 
N 
number 
PGI-S 
Patient Global Impression of Severity 
PGI-C 
Patient Global Impression of Change 
PK 
Pharmacokinetics 
PT 
Preferred term 
QD 
Once daily 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SRC 
Study Review Committee 
TEAE 
Treatment-emergent adverse event 
US 
United States of America 


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1 
REVISION HISTORY 
 
Revision No./ 
Date 1 
Author of 
Revision 2 
Section(s) 
Modified 
Description and/or Reason(s) for Revision 
 
 
 
 
 
 
 
 
1 Update the last revision dates on the cover page and the footer 
2 Provide first initial and last name 
 
 


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2 
INTRODUCTION 
2.1 Background  
Sofpironium bromide (BBI-4000) is a novel soft-anticholinergic ester analog of glycopyrrolate in 
development for the topical treatment of primary axillary hyperhidrosis.  
2.2 Rationale  
The pediatric pharmacokinetic (PK) and safety study (BBI-4000-CL-105), that precedes this 
long-term safety extension study, is a short treatment duration (7 days [±1 day]) PK study. The 
purpose of this study is to collect additional safety and tolerability information on children and 
adolescents following once daily (QD) sofpironium bromide gel, 15% treatment for up to 24 
weeks. Furthermore, subjects enrolled in Study BBI-4000-CL-105 may only begin to perceive 
improvement of symptoms near its conclusion. Therefore, subjects who complete Study BBI-
4000-CL-105 will be allowed the opportunity to participate in this long-term extension study 
(i.e., 24 weeks of treatment) in which they may potentially experience additional clinical benefit 
from sofpironium bromide gel, 15%. The data collected will further inform enhance the pediatric 
safety and tolerability profile of the study drug. 
This Statistical Analysis Plan (SAP) is based on the protocol for Study BBI-4000-CL-108, 
Version 0 (Original), dated 21 September 2018. 
3 
STUDY OUTLINE 
This multicenter, open-label extension study will evaluate the long-term safety, tolerability, and 
PK of sofpironium bromide gel, 15%, when applied (QD) for up to 6 months in pediatric subjects 
≥9 years to ≤17 years of age with axillary hyperhidrosis previously enrolled in Study BBI-4000-
CL-105.  
Following completion of the initial PK and safety study (Study BBI-4000-CL-105), subjects will 
be provided the opportunity to enter a 6-month open-label extension study. Subjects will be 
screened for eligibility at Day 8 of Study BBI-4000-CL-105 (last PK sample collection under 
BBI-4000-CL-105 study). Therefore, for participating subjects, the final treatment visit (i.e., Day 
8/Visit 4) of Study BBI-4000-CL-105 and the Screening/Enrollment visit (i.e., Week 0 [Day 1]) 
of Study BBI-4000-CL-108 (long-term extension study) will take place simultaneously. 
Subjects (parent/guardian) will be dispensed one container of sofpironium bromide gel, 15% 
each month at Visits 1-6. Subjects (and parent/guardian) will be instructed on the correct 
application procedure for sofpironium bromide gel, 15% (to be applied QD before bedtime to 
both axilla for up to 24 weeks). 
Vital signs, review of concomitant medications, assessment of adverse events (AEs), completion 
of patient-reported outcomes (Hyperhidrosis Disease Severity Measure-Axillary [HDSM-Ax] 
and Hyperhidrosis Disease Severity Measure-Axillary, Child [HDSM-Ax, Child] and Patient 
Global Impression of Severity [PGI-S]), and urine pregnancy tests (UPT) for all females will be 
done each visit. Application site tolerability will be assessed at all visits through the end of 
treatment (EOT) at Week 24 (Day 168 [±5 days]). Blood and urine for safety testing will be 
collected and analyzed at Week 4 (Day 28 [±3 days]) and Week 24 (Day 168 [±5 days]) for 
routine hematology, chemistry, and urinalysis parameters. Electrocardiograms (ECGs) will be 


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assessed at Week 0 (pre-dose, Day 1), Week 4 (Day 28 [±3 days]), and Week 24 (Day 168[ ±5 
days]). A PK sample will also be collected at Week 4 (Day 28 [±3 days]) and at Week 24 (Day 
168 [±5 days]). At Week 12 (Day [84 ±5 days]) and at the EOT at Week 24 (Day [168 ±5 days]), 
the subject will also complete the Patient Global Impression of Change (PGI-C). A final visit 
will be conducted 2 weeks after the last application of study drug. Clinically significant 
abnormal laboratory parameters and abnormal ECG noted at the previous visit, should be 
repeated at this visit. Comfort measures (e.g., topical analgesics and mechanical interference 
devices) may be used during all study blood collection events to reduce subject discomfort. 
A total of 8 scheduled visits will take place over approximately 26 weeks: Week 0 (Day 1), 
Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [±5 days]), Week 12 (Day 84 [±5 days]), Week 16 
(Day 112 [±5 days]), Week 20 (Day 140 [±5 days]), Week 24 (Day 168 [±5 days]), and Week 26 
(Day [182 ±5 days]). Subjects who prematurely discontinue study drug will complete the EOT 
(Week 24/Visit 7) visit.  
An internal Study Review Committee (SRC), comprising the Sponsor Medical Monitor, Lead 
Investigator and Contract Research Organization (CRO) Medical Monitor, will facilitate the 
management and identification of potential safety concerns, and will assess whether revisions to 
the study protocol and/or consent are required, and will evaluate the overall progress of the 
study. 
 
Figure 1 
Study Schematic 


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4 
SCHEDULE OF ACTIVITIES 
 
Description 
With Protocol Reference 
Screening/ 
Enrollment 
 
  
Treatment 
End of 
Treatment/Early 
Termination  
End of 
Study 
 
Week 
Week 0 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24 
Week 26 
Study Day (±days)/ 
Visit  
Day 1/ 
Visit 1 
Day 28 (±3)/ 
Visit 2 
Day 56 (±5)/ 
Visit 3 
Day 84 (±5)/  
Visit 4 
Day 112 (±5)/ 
Visit 5 
 
Day 140 (±5)/ 
Visit 6 
 
 
Day 168 (±5)/ 
Visit 7 
 
Day 182 (±5)/ 
Visit 8 
Consent/Assent 
Refer to Section 6.1 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
Refer to Sections 5.1 and 5.2 
X 
  
 
 
 
 
 
 
Demographics 
Refer to Section 6.2 
X a 
 
 
 
 
 
 
 
Height/Weight 
Refer to Section 6.5 
X a 
 
 
 
 
 
 
 
Abbreviated Physical 
Examination 
Refer to Section 6.4 
X b 
X 
 
 
 
 
X 
X 
Medical/Medication History  
Refer to Section 6.3 
X b 
 
 
 
 
 
 
 
Vital Signs 
Refer to Section 6.7 
X b 
X  
X 
X 
X 
X 
X 
X 
HDSM-Ax and HDSM-Ax, 
Child,  
Refer to Section 6.8 
X a 
X  
X 
X 
X 
X 
X 
X 
PGI-S Refer to Section 6.10 
X a,b 
X 
X 
X 
X 
X 
X 
X 
PGI-C Refer to Section 6.11 
 
 
 
X 
 
 
X 
 
Safety laboratory testing  
Refer to Section 6.12.4.2 
X a,b 
X 
 
 
 
 
X 
X d 
Pregnancy testing (females 
only) Refer to Section 
6.12.4.1 
X b 
X 
X 
X 
X 
X 
X 
 
PK sampling 
Refer to Section 6.12.5 
X b 
X c  
  
 
 
 
X c 
 


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Description 
With Protocol Reference 
Screening/ 
Enrollment 
 
  
Treatment 
End of 
Treatment/Early 
Termination  
End of 
Study 
 
Week 
Week 0 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24 
Week 26 
Study Day (±days)/ 
Visit  
Day 1/ 
Visit 1 
Day 28 (±3)/ 
Visit 2 
Day 56 (±5)/ 
Visit 3 
Day 84 (±5)/  
Visit 4 
Day 112 (±5)/ 
Visit 5 
 
Day 140 (±5)/ 
Visit 6 
 
 
Day 168 (±5)/ 
Visit 7 
 
Day 182 (±5)/ 
Visit 8 
12-lead ECG 
Refer to Section 6.8 
X b 
X 
 
 
 
 
X 
X d  
Concomitant Medications 
Refer to Section 6.13 
X b 
X 
X 
X 
X 
X 
X 
X 
AE Assessment 
Refer to Section 10  
X b 
X 
X 
X 
X 
X 
X 
X 
Application Site Tolerability 
Assessment 
Refer to Section 6.6 
X b 
X 
X 
X 
X 
X 
X 
 
Dosing, Refer to Sections 8.4 
and 8.5 and Study drug 
application and dosing diary 
card completion Refer to 
Appendix C  
  
 
Compliance  
Refer to Section 8.5 
X b 
X 
X 
X 
X 
X 
X 
 
Study Drug Dispensing 
Refer to Section 8.3 
X 
X 
X 
X 
X 
X 
 
 
ª  Baseline data (prior to first dose) collected under Study BBI-4000-CL-105 will be carried over to the current study. 
b Data collected at EOT (Day 8 [±1 day]) under Study BBI-4000-CL-105 will be carried over to the current study. 
c Collection ≥12 hours from evening application of drug. 
d  Only collect if abnormal at Visit 7/Early Termination Visit. 


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5 
STUDY DURATION 
Each subject will participate in the study for up to 26 weeks: 
• 
Screening (Day 1) 1 
• 
Treatment (24 weeks) 
• 
Follow-up (2 weeks after last dose) 
1 Subjects enrolled in Study BBI-4000-CL-105 opting to enroll in this extension study will 
continue receiving study drug in the extension study. The screening visit of Study BBI-
4000-CL-108 (Visit 1 [Day 0]) and EOT visit of Study BBI-4000-CL-105 (Day 8 [ ±1 
day]) will be conducted simultaneously. 
6 
STUDY POPULATON 
Subjects enrolled in this study will be males and females, ≥9 to ≤17 years of age, with 
axillary hyperhidrosis who participated in and completed Study BBI-4000-CL-105. 
7 
STUDY OBJECTIVES AND ENDPOINTS 
7.1 Objectives 
 Primary Objectives 
7.1.1.1 Safety 
To assess the long-term safety and tolerability of sofpironium bromide gel, 15% applied 
topically QD for up to 24 weeks in children and adolescent subjects, >9 to ≤17 years of age, 
with axillary hyperhidrosis.  
7.1.1.2 Pharmacokinetics 
To assess the systemic exposure (Ctrough) of sofpironium and its primary metabolite (BBI-
4010) following topical application of ~0.67 mL of sofpironium bromide gel, 15% applied 
topically to each axilla, QD for up to 24 weeks. 
 Exploratory Objectives 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on HDSM-Ax 
and HDSM-Ax, Child in pediatric subjects, ≥9 to ≤17 years of age, with axillary 
hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on 
Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Summary Questions; 
duration (No. 4) and severity (No. 5) in pediatric subjects, ≥9 to ≤17 years of age, with 
axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on PGI-S in 
pediatric subjects, ≥9 to ≤17 years of age, with axillary hyperhidrosis 
• 
To assess the effect of topically applied sofpironium bromide gel, 15% on PGI-C in 
pediatric subjects, ≥9 to ≤17 years of age, with axillary hyperhidrosis. 


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7.2 Endpoints 
 Primary Endpoints 
7.2.1.1 Safety 
• 
Incidence and severity of application site burning, itching, stinging, scaling and 
erythema 
• 
Incidence and severity of all AEs and their relationship to study drug 
• 
Incidence of clinically meaningful change from baseline in safety laboratory 
parameters, physical examination, 12-lead ECGs and vital signs 
• 
Proportion of subjects who discontinue treatment due to an AE 
7.2.1.2 Pharmacokinetics 
• 
Determination of plasma concentrations (Ctrough) of sofpironium and BBI-4010 at 
Week 4 and Week 24 (EOT) following 24 weeks of QD topical application of 
sofpironium bromide gel, 15%. 
 Exploratory Endpoints 
• 
Change of HDSM-Ax (≥12 years of age) or HDSM-Ax, Child (≥9 to <12 years of age) 
from baseline to EOT 
• 
Change of HDSM-Ax Summary Questions; duration (No. 4) and severity (No. 5) from 
baseline to end of treatment. 
• 
Change of PGI-S from baseline to EOT 
• 
PGI-C at Week 12 (Day 84) and EOT 
7.3 Study Assessments 
 Safety 
• 
Adverse events at all visits 
• 
Local application site tolerability assessments (including burning, itching, stinging, 
scaling and erythema) at all visits through Week 24 [Day 168] and Week 26 (Day 
182), if applicable 
• 
Vital signs (heart rate [HR], blood pressure, respiratory rate and temperature) at all 
visits through and including Week 26 
• 
12-lead ECG at Week 0 (Day 1), Week 4 (Day 28), Week 24 (Day 168), and Week 26 
(Day 182), if applicable 
• 
Laboratory testing (hematology, chemistry and urinalysis) at Week 0 (Day 1), Week 4 
(Day 28), Week 24 (Day 168), and Week 26 (Day 182), if applicable 
• 
Pregnancy test (females) at all visits through and including Week 26 (Day 182) 


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• 
Abbreviated physical examination at all visits through and including Week 26 (Day 
182) 
 Pharmacokinetics 
• 
Plasma samples will be collected ≥12 hours after the last dose on Week 0 (Day 1) [per 
Day 8/Visit 4 of Study BBI-4000-CL-105], Week 4 (Day 28 [±3 days]), and Week 24 
(Day 168 [±5 days]). 
 Efficacy 
• 
HDSM-Ax or HDSM-Ax, Child as measured at all visits through and including Week 
26 (Day 182 [±5 days]). 
• 
HDSM-Ax or HDSM-Ax, Child Summary Questions; duration (No. 4) and severity 
(No. 5) as assessed by the subject at all visits through and including Week 24 (Day 
168) 
• 
PGI-S, as measured by the subject at all visits through and including Week 26 (Day 
182 [±5 days]). 
• 
PGI-C as measured by the subject at Week 12 (Day 112 [±5 days]) and Week 24 (Day 
168 [±5 days]). 
8 
DOSING AND COMPLIANCE 
All subjects will receive active study drug. One dose of sofpironium bromide gel, 15% will 
be applied topically using the supplied applicator to each axilla QD at approximately the 
same time before bedtime for up to 24 weeks. Sofpironium bromide gel is packaged in 
airless, multi-dose, metered pump containers. Each administration of sofpironium bromide 
gel, 15% is ~0.67 mL and contains 86.5 mg of sofpironium bromide, for a total daily dose 
when applied to both axillae of 173 mg. 
The subject and/or the parent(s)/guardian(s) will record that the study drug was applied to 
each axilla (right and left) and when the subject applied the study drug in the dosing diary 
card. The site personnel will review the dosing diary card and weigh the pump container, 
with cap on, at Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [±5 days)], Week 12 (Day 84 
[±5 days]), Week 16 (Day 112 [±5 days]), Week 20 [Day 140 [±5 days]), and Week 24 (Day 
168 [±5 days]).  
9 
BREAKING THE BLIND 
Not applicable as this is an open-label study. 
10 STUDY REVIEW COMMITTEE 
An internal SRC, comprising the Sponsor Medical Monitor, Lead Investigator and CRO 
Medical Monitor, will facilitate the management and identification of potential safety 
concerns and will assess whether revisions to the study protocol and/or consent are required 
and will evaluate the overall progress of the study. 


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11 
SAMPLE SIZE 
Sample size is based on the planned enrollment under Study BBI-4000-CL-105. Up to 24 
subjects may participate in this study.  
12 GENERAL CONSIDERATIONS FOR DATA ANALYSIS  
12.1  Analysis Populations 
Two populations will be used for analysis: Safety and PK. The definition of these 
populations follows: 
• 
Safety Population: All enrolled subjects who applied at least one dose of study drug 
and have at least one post-baseline safety assessment. 
• 
Pharmacokinetic Population: All enrolled subjects who applied at least one dose of 
study drug and have at least one quantifiable PK sample for analysis. 
12.2 Interim Analysis 
No interim analyses are planned. 
12.3 General Considerations for Analysis 
 Safety and Efficacy Analysis 
• 
The Safety population will be used for evaluation of safety and efficacy parameters. 
• 
Analyses of safety and efficacy data will be performed in Statistical Analysis System 
(SAS) software version 9.2 or higher (SAS Institute Inc., 2008).  
• 
The final analysis will be conducted after all subjects have completed the study and 
the database is locked. Listings will report all data collected in the database. 
• 
If a data table is sparse, only a listing will be presented. Unless otherwise stated, all 
listings will be sorted by subject number and visit date. Continuous variables will 
generally be summarized using means, medians, standard deviation (SD), minimum, 
and maximum. Discrete variables will be summarized by frequency and percentages.  
• 
Summary tables will indicate the number of subjects with complete data for each 
measurement, event, or outcome.  
• 
Data will be summarized in plots organized by time point and over time.  
• 
For multiple or repeated assessments for the same visit, the latest assessment will be 
included in the summary tables.  
• 
Summary tables will only include data from scheduled visits.  
• 
Data from unscheduled visits will be included in the listings. 
• 
If additional analyses are required to supplement the planned analyses, they may be 
performed and will be identified in the appropriate section of the clinical study report 


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(CSR). Any substantial deviations from the planned SAP will updated in the SAP and 
approved. 
 Pharmacokinetics 
• 
The PK population will be used for evaluation of PK parameters.  
• 
All plasma PK parameter calculations (Ctrough values) will be performed using actual 
time points (actual date and time of each blood draw) calculated relative to the time of 
study drug administration.  
• 
Graphical comparison of Ctrough values (collected ≥12 hours after the prior dose) on 
Week 0 (Day 1), Week 4 (Day 28 ±3 days), and Week 24 (Day 168 [±5 days]) will be 
used to assess steady state levels.  
• 
All descriptive analyses and generation of tables, listings and figures, will be 
performed using a validated installation of Phoenix WinNonlin® version 8.0 
(Pharsight, Cary, North Carolina, USA) as part of a 21 CFR Part 11 compliant 
database system (Pharsight Knowledgebase Server “PKS”).  
• 
The final analysis will be conducted after all subjects have completed the study, all PK 
samples collected, have been analyzed, and the database is locked.  
• Subject demographics, baseline characteristics, disposition, dosing dates and dosing 
times, and compliance data necessary to support analysis of PK, will be imported 
(SAS datasets) from the clinical safety and efficacy database (eCRF data). 
• If additional analyses are required to supplement the planned PK analyses, they may 
be performed and will be identified in the appropriate section of the CSR. Any 
substantial deviations from the planned SAP will updated in the SAP and approved. 
 Handling of PK Concentration Values Below the Limit of Quantification  
The lower limit of quantification of the assay in plasma is 0.0555 ng/mL for both 
sofpironium and BBI-4010. Concentrations that are reported as below the limit of 
quantitation will be set to 0 for the calculation of the descriptive statistics for the drug 
concentration summary.  
 Handling of Missing PK Sampling or Concentration Data 
Missing sampling or concentration values will not be imputed but left missing in the 
calculation of mean concentrations. Concentrations that are not reportable due to technical 
artifact or ambiguity will be treated as missing values. If the actual sampling time is missing, 
but a valid concentration value has been measured, the scheduled protocol time will be used 
for the calculation of mean concentration. 
 Handling of PK Outliers 
On a case by case basis, it may be necessary to exclude individual bioanalytical data from the 
calculation of mean concentrations because they are erroneous, abnormal or appear 
implausible to the pharmacokineticist in charge of the analysis. Any excluded data will be 


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flagged in the individual data listings. The reason for exclusion will also be documented. If 
the exclusion has a meaningful impact on the overall interpretation of the results, it will be 
discussed with the Sponsor. 
 Handling of Actual vs. Planned PK Sampling Timepoints 
Actual post-dose time will be used in the Tables and Listings of individual Ctrough values. The 
PK sample collection window (≥12 hrs from previous dose and prior to next dose) will be 
used to summarize descriptive statistics for Ctrough values.  
 Handling of Individual PK Data and Summary Data Formats 
The actual values as provided from the bioanalytical laboratory will be displayed as 
individual concentration-time listings. Drug concentrations will be used to calculate the mean 
using descriptive analysis. For summary tables, the descriptive statistics will be rounded to 
one more digit than the individual values for the arithmetic mean, SD, median and geometric 
mean, and to the same number of digits for the minimum and maximum values. The number 
of non-missing observations (N) will be reported as an integer number. The coefficient of 
variation (CV) (%) and geometric CV% will be reported as a percentage (CV*100) as an 
integer number. 
12.4 Derived and Transformed Data 
Baseline 
The Baseline (Day 1, pre-dose) measurement of a variable is the latest non-missing 
measurement before the first dose of study drug in Study BBI-4000-CL-105 
Age  
Age (in completed years) will be calculated for each subject as: 
Age (years) = (Date of Screening visit – Date of Birth + 1) / 365.25 
12.5 Assessment Days and Windows 
The listings will include all assessments. The following assessment windows are established:  
• 
Visit 1: Screening/Enrollment (Week 0 [Day 1]) 
• 
Visit 2: Week 4 (Day 28 [±3 days]) 
• 
Visit 3: Week 8 (Day 56 [±5 days]) 
• 
Visit 4: Week 12 (Day 84 [±5 days]) 
• 
Visit 5: Week 16 (Day 112 [±5 days]) 
• 
Visit 6: Week 20 (Day 140 [±5 days]) 
• 
EOT/Early Termination Visit 7: Week 24 (Day 168 [±5 days])  
• 
End of Study (EOS) Visit 8: Week 26 (Day 182 [±5 days]) 


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12.6 Missing Safety and Efficacy Data  
Adverse events recorded with ambiguous or missing start dates and times will be assumed to 
have started after the first dose of study drug on Day 1 of Study BBI-4000-CL-105. 
Consequently, such AEs will be included in all summaries of treatment-emergent adverse 
events (TEAE). Start and end dates and times for AEs will be listed as collected. 
Where the start or end date of a concomitant medication is ambiguous or missing, the 
medication will be assumed to have been started before and continued after the first dose of 
study drug in Study BBI-4000-CL-105. That is, the medication will be listed as both prior 
and concomitant and included in the summary table of concomitant medications.  
All other cases of missing or invalid data will be treated as missing and will not be imputed. 
Start and end dates for concomitant medications will be listed as collected. 
12.7 Medication and Adverse Event Coding Dictionaries 
• 
Concomitant medications are coded using the March 2018 version of the World 
Health Organization Drug Coding Dictionary (WHODD).  
• 
Adverse events are coded using version 21.0 of the Medical Dictionary for Regulatory 
Activities (MedDRA). 
12.8 Protocol Deviations and Violations 
Subject data will be examined for evidence of protocol deviations and violations in order to 
assess how well the investigators followed the protocol. A protocol deviation is a variation 
from processes or procedures defined in a protocol. Deviations usually do not preclude the 
overall evaluability of subject data and are often acknowledged and accepted in advance by 
the Sponsor. A protocol violation is a significant departure from processes or procedures that 
were required by a protocol. Violations often result in data that are not deemed evaluable for 
PK or efficacy analysis and may require that the subject(s) who violate the protocol be 
discontinued from the study. 
A sponsor designee will perform a final review of the list of protocol deviations and 
violations prior to database lock and according to data available on the eCRF to adjudicate 
the categorization of the protocol deviations and violations. 
13 STATISTICAL ANALYSIS 
13.1 Baseline Parameters, Demographics, Medical History, Hyperhidrosis History, 
Concomitant Medications, Disposition and Drug/Alcohol Screening, and 
Pregnancy Testing  
• 
The total number of subjects enrolled in the study. 
• 
Subject demographics and baseline characteristics will include, date of birth, gender, 
race, ethnicity, height and weight, and age at onset and duration of hyperhidrosis, will 
be summarized and listed. Descriptive statistics (mean, SD, median, minimum, and 
maximum for numerical variables; count and percentage for categorical variables) will 
be presented where applicable.  


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• 
Subject medical, hyperhidrosis and medication history will be listed by MedDRA 
system organ class and preferred term (PT). A listing sorted by subject number, 
MedDRA system organ class and PT, and onset date will also be presented. 
• 
Subject medication history will be mapped according to the WHODD. 
• 
A listing of subject disposition will include start date and time of first study drug 
application in the extension study. 
• 
The number of subjects who complete treatment (Day 168 [±5 days], EOT) will be 
summarized and listed. 
• 
The number of subjects who complete study (Day 182 [±5 days], EOS) will be 
summarized and listed. 
• 
The number of subjects who prematurely discontinue from the study and reason for 
discontinuation will be summarized and listed. The number of subjects who 
prematurely withdraw from study drug but remaining in the study will be summarized. 
• 
Concomitant medications (start date on or after Day 1 of Study BBI-4000-CL-105) 
will be summarized using descriptive statistics.  
• 
Use of concomitant medications (chronic medications or as needed medications e.g., 
acetaminophen, EMLA cream) are permitted during the screening and active study 
period (Day 1 through Day 168 [±5 days]) and will be recorded on the eCRF.  
• 
Changes in concomitant medication usage will be recorded on the eCRF. If the reason 
for change is related to an AE, the event will be recorded in as an AE in the eCRF.  
• 
Concomitant medications will be mapped according to the WHODD and will be 
presented in data listings. 
• 
Drug and alcohol screen by visit will be listed. 
• 
Pregnancy test (positive or negative) by visit will be listed. 
13.2 Drug Exposure and Treatment Compliance 
• 
Study drug applications made or missed, and location (right and left axilla) will be 
recorded on the dosing diary card and data will be entered in the eCRF. Study drug 
applications and application location by day and by visit will be summarized. 
• 
Study drug compliance will be evaluated at each visit during the treatment period. The 
site personnel will review the dosing diary card and weigh the pump container, with 
cap on, at Week 4 (Day 28 [±3 days]), Week 8 (Day 56 [±5 days]), Week 12 (Day 84 
[±5 days]), Week 16 (Day 112 [±5 days]), Week 20 (Day 140 [±5 days]), and Week 
24 (Day 168 [±5 days]). Amount (by weight) of study drug used by visit and overall 
difference in weight between Day 1 and final dose application on Day 168 [±5 days], 
will be summarized. 


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13.3 Primary Analyses 
 Safety  
Safety evaluations will consist of AEs, application site local tolerability, physical 
examinations, vital signs, ECGs, and laboratory measurements (hematology, chemistry, and 
urinalysis).  
• 
Adverse events: 
o Adverse events will be mapped to standard terms, i.e., MedDRA System 
Organ Class and Preferred Term. 
o Adverse events that occurred during the screening period will be listed 
separately and will not be included in the AE tabulations. 
o Adverse events that start on or after first dose will be considered a TEAE. At 
each post-baseline visit, the number and proportion of subjects reporting any 
given TEAE will be tabulated by severity; each subject will be counted only 
once according to the worst severity reported up to the current visit. Separate 
tables will be constructed for (a) all reported TEAEs, (b) protocol treatment 
related TEAEs, (c) serious TEAEs, and (d) TEAEs leading to protocol 
treatment discontinuation. 
• 
At each applicable visit, local tolerability (burning, itching, stinging, scaling, and 
erythema at either axilla) will be described by severity as defined in Appendix E. 
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) presented by parameter and visit. 
• 
Vital signs will be summarized similarly as for laboratory parameters but without shift 
tables. 
• 
Laboratory parameters will be descriptively summarized (mean, SD, median, 
minimum, maximum) for values at each visit and for changes from baseline at each 
subsequent visit. In addition, at each post baseline visit, parameter status (low, normal, 
high) will also be summarized as shift tables vs. baseline status.  
• 
Descriptive statistics and/or frequency tables will be prepared as appropriate for 
physical examinations, and ECG (HR, QTcF, PR, and QRS) parameters, and 
abnormalities (e.g., normal; abnormal, not clinically significant; abnormal, clinically 
significant).  
• 
Concomitant medications will be mapped according to the World Health Organization 
Drug Dictionary (WHODD) and will be presented in data listings. 
 Pharmacokinetics 
• Plasma concentrations of sofpironium and BBI-4010, will be determined using 
validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) 
analytical methods. The lower limit of quantification (LLQ) of the assay in plasma is 


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0.0555 ng/mL for both sofpironium and BBI-4010. Specifics of the analytical 
procedures will be provided in separate bioanalytical documentation. 
• Individual plasma Ctrough values of sofpironium and BBI-4010 will be summarized 
descriptively using the arithmetic mean, SD, CV (%), median, minimum and 
maximum. Mean (±SD) Ctrough values will also be presented graphically by week to 
assess exposure, accumulation and steady state 
13.4 Exploratory Analysis 
• 
Descriptive summaries will be provided for HDSM-Ax and HDSM-Ax, Child, 
Summary Questions (No. 4 and No. 5) and PGI-S. Mean changes from baseline and 
observed values will be summarized by time point. 
• 
For HDSM-Ax and HDSM-Ax, Child, the mean of the items in Section No. 1, No. 2, 
and No. 3 will be calculated for every subject at each time point. The mean will be 
derived by taking the total score and dividing it by the number of questions answered. 
Subjects must answer ≥6 of the 11 sub-items to be evaluable for HDSM-Ax or 
HDSM-Ax, Child total score. Observed values and changes from baseline at each time 
point will be summarized and plotted over time using descriptive statistics. 
• 
For the HDSM-Ax or HDSM-Ax, Child Summary Questions (No. 4 and No. 5), the 
score for each question, will be reported for every subject at each time point and will 
be summarized and plotted over time using descriptive statistics.  
• 
For PGI-S, the score will be reported for every subject at each time point and will be 
summarized and plotted over time using descriptive statistics. 
• 
For PGI-C, the score will be reported for every subject at Week 12 and Week 24 
(EOT) and will be summarized and plotted over time using descriptive statistics. 
• 
Missing data will not be imputed for any analyses. 
14 REFERENCES 
None 


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15  APPENDICES 
15.1 Appendix A: Preliminary Table of Contents for Tables, Listings, Figures for 
Safety and Efficacy 
Tables: Demographics, Baseline Characteristics, Analysis Populations/Subject 
Accountability, Medical History, Hyperhidrosis History, Concomitant Medications 
Table 14.1.1  
Analysis Populations / Subject Accountability 
Table 14.1.2.1  Demographics, Baseline Characteristics - Safety 
Table 14.1.2.2  Demographics and Baseline Characteristics- PK 
Table 14.1.3  
Medical History and Hyperhidrosis History – Safety 
Table 14.1.4  
Concomitant Medications - Safety 
Efficacy Tables – Safety Population 
14.2.1  Summary of HDSM-Ax and HDSM-Ax, Child Measurements and Changes from 
Baseline (All) 
14.2.2  Summary of HDSM-Ax and HDSM-Ax, Child Anchors and Change from Baseline 
over Time (All) 
14.2.3  Summary of PGI-S score and Change from Baseline over Time (All) 
14.2.4  Summary of PGI-C score and Change from Baseline over Time (All) 
Efficacy Figures – Safety Population 
Figure 14.2.1  Mean Changes from Baseline Over Time in HDSM-Ax, Child and HDSM-
Ax (All) 
Figure 14.2.2 Mean Observed Values over Time in HDSM-Ax, Child and HDSM-Ax (All) 
Figure 14.2.3  Mean Changes from Baseline Over Time in HDSM-Ax, Child and HDSM-
Ax Anchors (All) 
Figure 14.2.4  Mean Observed Values over Time in HDSM-Ax, Child and HDSM-Ax 
Anchors (All) 
Figure 14.2.5  Mean Changes from Baseline Over Time in PGI-S (All) 
Figure 14.2.6  Mean Observed Values over Time in PGI-S (All) 
Figure 14.2.7  Mean Changes from Baseline Over Time in PGI-C (All) 
Figure 14.2.8  Mean Observed Values over Time in PGI-C (All) 
Safety Data – Safety Population 
Displays of Adverse Events 


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Table 14.3.1.1  
Incidence of Treatment Emergent Related Adverse Events by Severity 
Table 14.3.1.2  
Incidence of Serious Treatment Emergent Adverse Events by Severity 
Table 14.3.1.2  
Incidence of Serious Treatment Emergent Related Adverse Events by 
Severity 
Abnormal Laboratory Value Listing (each Subject) – Safety Population 
Table 14.3.4.1  
Clinical Chemistry Laboratory Summary 
Table 14.3.4.2  
Clinical Chemistry Laboratory Values Shift Tables 
Table 14.3.4.3  
Hematology Laboratory Summary 
Table 14.3.4.4  
Hematology Laboratory Values of Interest Shift Tables 
Table 14.3.4.5.1  Urinalysis Laboratory Summary (Continuous Results) 
Table 14.3.4.5.2  Urinalysis Laboratory Summary (Categorical Results) 
Table 14.3.4.5.3  Incidence and Severity of Application Site Burning – Shift Table 
Table 14.3.4.5.4  Incidence and Severity of Application Site Itching – Shift Table 
Table 14.3.4.5.5  Incidence and Severity of Application Site Dryness – Shift Table 
Table 14.3.4.5.6  Incidence and Severity of Application Site Scaling – Shift Table 
Table 14.3.4.5.7  Incidence and Severity of Application Site Erythema – Shift Table 
Other Safety Data Summaries – Safety Population 
Table 14.3.5.1  Summary of Vital Signs  
Table 14.3.5.2  Summary of ECG parameters 
Table 14.3.5.3  Incidence of Out of Range ECG parameters 
Table 14.3.5.4  Summary of Status of ECGs (normal, abnormal not clinically significant, 
abnormal clinically significant) 
Subject Data Listings – Safety Population 
Discontinued Subjects 
Listing 16.2.1.1.1  Subject Disposition (Completion or Discontinuation) & Compliance 
Listing 16.2.1.1.2  Subject Disposition (visit dates) 
Listing 16.2.1.2  
Discontinued Subjects: Adverse Events 
Protocol Deviations – Safety Population 
Listing 16.2.2.1  
Listing of Protocol Deviations 
Listing 16.2.2.2  
Eligibility: Inclusion/Exclusion Criteria 


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Subjects Excluded from the Efficacy Analysis 
Listing 16.2.3.1  
Listing of Subjects Excluded from the Efficacy Analysis 
Demographic and Baseline Characteristics Data – Safety Population 
Listing 16.2.4.1  
Demographics and Baseline Characteristics 
Listing 16.2.4.2  
Medical History and Hyperhidrosis History  
Listing 16.2.4.3  
Prior and Concomitant Medications 
Compliance and/or Drug Concentration Data – Safety Population 
Listing 16.2.5.1  
Investigational Product Accountability 
Listing 16.2.5.2  
Investigational Product Exposure 
Individual Efficacy Response Data – Safety Population 
Listing 16.2.6.1  
Efficacy HDSM-Ax and HDSM-Ax, Child at Baseline and Change from 
Baseline 
Listing 16.2.6.2  
Efficacy PGI-S at Baseline and Change from Baseline 
Adverse Event Listings (each Subject) – Safety Population 
Listing 16.2.7.1  
Adverse Event Listing 
Listing 16.2.7.2  
Serious Adverse Event Listing 
Listing 16.2.7.3  
Vital Signs 
Listing 16.2.7.4  
ECGs 
Listing 16.2.7.5  
ECG Abnormalities 
Listing 16.2.7.6  
Physical Examination 
Listing 16.2.7.7  
Application site burning, itching, dryness, scaling and erythema 
Listing of Individual Laboratory Measurements by Subject - Safety Population 
Listing 16.2.8.1  
Clinical Chemistry Laboratory Measurements 
Listing 16.2.8.2  
Hematology Laboratory Measurements 
Listing 16.2.8.3  
Urinalysis Laboratory Measurements 
Listing 16.2.8.3  
Drug and Alcohol Screen 
Listing 16.2.8.4  
Pregnancy Testing 
Other Data Listings – Safety Population, patients with respective comments 
Listing 16.2.9.1  
Case Report Form General Comments 


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Listing 16.2.9.2  
Laboratory Data Comments 
Listing 16.2.9.3  
ECG Data Comments 
 


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15.2 Appendix B: Preliminary Table of Contents for Tables, Listings, Figures for PK 
Tables 
Table 14.x.x.1  Summary of Mean (SD), CV%, Median, Min and Max Sofpironium Plasma 
Concentrations (Ctrough values) by Week 
Table 14.x.x.2  Summary of Mean (SD), CV%, Median, Min and Max Metabolite Plasma 
Concentration (Ctrough values) by Week 
Listings 
Listing 16.x.x.1  Individual Pharmacokinetic Sampling Times and Plasma Concentrations 
(Ctrough) values of Sofpironium by Week  
Listing 16.x.x.2  Individual Pharmacokinetic Sampling Times and Plasma Concentrations 
(Ctrough) of Primary Metabolite by Week  
Figures 
Table of Content for Figures  
Figure 14.x.x.1  Mean (±SD) Sofpironium Plasma Concentrations (Ctrough) versus Week 
(Linear Scale)  
Figure 14.x.x.2  Mean (±SD) Primary Metabolite Plasma Concentrations (Ctrough) versus 
Week (Linear Scale)  
Figure 14.x.x.3  Overlaid Individual Sofpironium Plasma Concentrations (Ctrough) versus 
Week (Linear Scale)  
Figure 14.x.x.4  Overlaid Individual Primary Metabolite Plasma Concentrations (Ctrough) 
versus Week (Linear Scale)  
 


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15.3 Appendix C: HDSM-Ax, Child (≥9 to <12 years of age) 
 
 


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15.4 Appendix D: HDSM-Ax (≥12 years of age) 


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15.5 Appendix E: Application Site Tolerability Assessments 
These assessments are to be performed for each axilla individually. The designation of 
“Right Axilla” or “Left Axilla” in the source documents and eCRFs 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): As reported by the Subject to the Investigator, the severity of 
any symptoms of burning, stinging or itching at the application-site within the previous 24 
hours and further any such symptoms persisting longer than 1 hour following study drug 
application will be described specifically by severity using the following standardized scales: 
Score 
Burning 
Stinging 
Itching 
0 = Absent 
Normal, no discomfort 
Normal, no discomfort 
Normal, no discomfort 
1 = Minimal 
An awareness, but no 
discomfort  
An awareness, but no 
discomfort  
An awareness, but no 
discomfort  
2 = Mild 
Noticeable discomfort 
causing intermittent 
awareness 
Noticeable discomfort 
causing intermittent 
awareness 
Noticeable discomfort 
causing intermittent 
awareness 
3 = Moderate 
Noticeable discomfort 
causing continuous 
awareness 
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 
Definite discomfort causing 
continuous awareness, 
interfering occasionally 
with normal daily activities 
Local Tolerability (Investigator): The Investigator will assess the drug-application site for 
the existence of significant local symptoms. Significant local symptoms are defined as those 
not ordinarily observed following application of a topical product. The following 
standardized scales will be used to describe specifically the severity of any erythema or 
scaling:  
Score 
Scaling 
Erythema 
0 = Absent 
No scaling 
No redness 
1 = Minimal 
Fine scaling, barely perceptible 
Faint red or pink coloration, barely 
perceptible 
2 = Mild 
Slight scaling, noticeable only with light 
scratching 
Light red or pink coloration 
3 = Moderate 
Definitely noticeable scaling 
Medium red coloration 
4 = Severe 
Extensive scaling 
Beet red coloration