A Confirmatory Safety and Efficacy Study of BBI-4000 in Subjects With Axillary Hyperhidrosis

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

Detailed Description
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This is a Multicenter, Randomized, Double Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of 3 concentrations of Topically Applied BBI-4000 in Subjects with Axillary Hyperhidrosis. Safety will be assessed through collection of vital signs, adverse events, local skin responses, hematology, serum chemistry laboratory testing and urinalysis.

Official Title
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A Multicenter, Randomized, Double-Blinded, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of 3 Concentrations of Topically Applied BBI-4000 (Sofpironium Bromide) Gel in Subjects With Axillary Hyperhidrosis

Conditions
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Hyperhidrosis

Intervention / Treatment
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* Drug: BBI-4000 gel, 5%
* Drug: BBI-4000 gel, 10%
* Drug: BBI-4000 gel, 15%
* Drug: Vehicle (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject ≥ 18 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, (c) HDSS of 3 or 4 and (d) a minimum GSP of 50 mg is 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(s). 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 potent inhibitors of cytochrome P450 CYP3A and CYP2D6. Use of any cholinergic drug (e.g. bethanechol) within 30 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. History or presence of supraventricular tachycardia, ventricular arrhythmias, atrial fibrillation or atrial flutter.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BBI-4000 gel, 5%<br>BBI-4000 gel, 5% applied once to each axilla daily | Drug: BBI-4000 gel, 5%<br>* BBI-4000 gel, 5% applied once to each axilla daily<br>* Other names: BBI-4000 Low Concentration;|
| Experimental: BBI-4000 gel, 10%<br>BBI-4000 gel, 10% applied once to each axilla daily | Drug: BBI-4000 gel, 10%<br>* BBI-4000 gel, 10% applied once to each axilla daily<br>* Other names: BBI-4000 Medium Concentration;|
| Experimental: BBI-4000 gel, 15%<br>BBI-4000 gel, 15% applied once to each axilla daily | Drug: BBI-4000 gel, 15%<br>* BBI-4000 gel, 15% applied once to each axilla daily<br>* Other names: BBI-4000 High Concentration;|
| Placebo Comparator: Vehicle<br>Placebo, applied once to each axilla daily | Drug: Vehicle (Placebo)<br>* Placebo, applied once to each axilla daily<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Score From Baseline to End of Therapy | 11 question evaluation tool to assess the effect of BBI-4000 gel, 5%, 10% and 15 % on hyperhidrosis disease severity measures in subjects with axillary hyperhidrosis. Two questions measured the frequency (since yesterday) of underarm sweating outcomes. The range of responses included increasing frequency scale: None of the time (0); A little of the time (1); Some of the time (2); Most of the time (3); All of the time (4). The next seven questions measured the severity of underarm sweating outcomes. Range in increasing severity: I did not experience this (0); Mild (1); Moderate (2); Severe (3); Very Severe (4). The last two questions measured the need to change or clean from underarm sweating. Range in increasing degree of need: Not at all (0); Slight (1); Moderate (2); Strong (3); Very Strong (4). The mean was derived by taking the total score and dividing by the number of questions answered. A negative LSM reflects a reduction, decrease or measured improvement in HDSM-Ax | overall  6 Weeks, as listed in description includes: Baseline-Visit 1, Visit 4 and End of Therapy Visit - Days 41, 42, 43. | 
| Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Subjects reporting more than one adverse event are counted only once using the highest severity. | Treatment initiation through end of treatment ( 42 days) and subsequent safety f/u ( 14 days following end of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Measured weight of the amount of sweat produced by Visit Method of calculating average for Baseline, End of Therapy, and End of Therapy Imputed. Baseline GSP was defined as the mean of any available Visit 2, Visit 3, and Visit 4 values (occurring Days -21 to -7 relative to Day 1 Baseline) End of Therapy is defined as the mean of any available Day 41, Day 42, and Day 43 values. | Visit 2, 3, and 4 timepoints were reported Days -21 to -7, relative to Visit 5/ Day 1/Baseline, Days 8, 15, 22, 29, 36, 41, 42, 43, and 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sweat gland disease, sweating, underarm