Safety and Efficacy Study of Sofpironium Bromide in Subjects With Axillary Hyperhidrosis (BBI-4000-CL-301)

Study Overview
=================
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. Current therapies have limited effectiveness, significant side effects, and can be invasive and costly. Sofpironium bromide (BBI-4000) is a novel soft-drug in development for the topical treatment of hyperhidrosis. This Phase 3 study will assess the safety and efficacy of sofpironium bromide, 15% gel versus vehicle (2 treatment arms), applied for the treatment of axillary hyperhidrosis.

Detailed Description
-----------------
This is a multicenter, randomized, double-blind, vehicle-controlled study to evaluate the safety and efficacy of topically applied sofpironium bromide, 15% gel in subjects with axillary hyperhidrosis. Safety will be assessed through collection of vital signs, adverse events, local skin responses, hematology, serum chemistry laboratory testing and urinalysis. A maximum of 350 subjects will be randomized to receive either sofpironium bromide gel, 15% or vehicle. Adverse events, vital signs, and local tolerability assessments will be collected at visits across the study. 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 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 13 scheduled visits to take place over approximately 11 to 15 weeks.

Official Title
-----------------
A Multicenter, Randomized, Double-Blinded, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of Topically Applied Sofpironium Bromide Gel, 15% in Subjects With Axillary Hyperhidrosis

Conditions
-----------------
Axillary Hyperhidrosis

Intervention / Treatment
-----------------
* Drug: Sofpironium Bromide Gel, 15%
* Drug: Vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subject ≥ 9 years of age. Diagnosis of primary axillary hyperhidrosis that meets the following criteria: (a) symptoms of hyperhydrosis for at least 6 months' duration, (b) HDSM-Ax of 3 - 4 and (c) a minimum GSP of 50 mg in each axilla with a combined total of at least 150 mg. The ability to understand and follow all study-related procedures including study drug administration. Sexually active female of childbearing potential (FOCBP)* must agree to periodic pregnancy testing and use a medically acceptable method of contraception while receiving protocol-assigned product. Exclusion Criteria: In the Investigators opinion, any skin or subcutaneous tissue conditions of the axilla(e). Prior use of any prohibited medication(s) or procedure(s) within the specified timeframe for the treatment of axillary hyperhidrosis. 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. Use of any cholinergic drug (e.g. bethanechol) within 28 days. Known cause of hyperhidrosis or known history of a condition that may cause hyperhidrosis (i.e., hyperhidrosis secondary to any known cause such hyperthyroidism, diabetes mellitus, medications, etc.). Subjects with unstable diabetes mellitus or thyroid disease, history of renal or hepatic impairment, malignancy glaucoma, intestinal obstructive or motility disease, obstructive uropathy, myasthenia gravis, BPH, neurological or psychiatric conditions, Sjögren's or Sicca syndrome, or cardiac abnormalities that may alter or exacerbate sweat production by the use of anticholinergics in the investigator's opinion. Subjects with known hypersensitivity to glycopyrrolate, anticholinergics, or any of the components of the topical formulation. Subject is pregnant, lactating or is planning to become pregnant during the study.

Ages Eligible for Study
-----------------
Minimum Age: 9 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Sofpironium bromide, 15% gel, once per day | Drug: Sofpironium Bromide Gel, 15%<br>* Active<br>* Other names: BBI-4000 Gel, 15%;|
| Placebo Comparator: Vehicle<br>Vehicle gel, once per day | Drug: Vehicle<br>* Vehicle gel<br>* Other names: BBI-4000 Gel, 0%;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants with treatment emergent adverse events | Summarized by MedDRA LLT with a 3 point severity scale of mild, moderate and severe | Through study completion (6 weeks). | 
| Change in Hyperhidrosis Disease Severity Measure-Axillary score | Change in score from baseline to end of treatment of an 11 question patient reported outcome assessment, each question has a 5 point response (range 0 [better] - 4 [worse]). | 6 weeks | 
| Gravimetric sweat production | Change in the measured weight (mg) of axillary (right+left axillae) sweat production from baseline to end of study. | 6 weeks |