A Safety Study of BBI-4000 Gel in Pediatric Patients With Axillary Hyperhidrosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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 Age 9-17 Years Previously Enrolled in BBI-4000-CL-105

Conditions
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Primary Axillary Hyperhidrosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject ≥9 to <17 years of age in good general health. Diagnosis of primary axillary hyperhidrosis that meets all the following criteria: (a) HDSM-Ax of 2 - 4 inclusive at both the Screening Visit (Visit 1) and Baseline Visit (Visit 2). (b) Symptoms of axillary hyperhidrosis for greater than or equal to 6 months' duration prior to enrollment. Exclusion Criteria: In the Investigator's opinion, any skin or 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). Prior use of any prohibited medication(s) or procedure(s) within the specified timeframe for the treatment of axillary hyperhidrosis: (a) Botulinum toxin to the axillary area within 9 months of enrollment. (b) Axillary thermolysis, sympathectomy or surgical procedures of the axillary area at any time in the past. (c) Serotonergic agonist (or drugs that increase serotonin activity including SSRIs), beta-blocker, alpha-adrenergic agonist (clonidine), dopamine partial agonist or tricyclic antidepressant treatment within 30 days of enrollment. However, if a subject has been on a stable dose (in the opinion of the PI) of any of these medications and has not had a recent change in hyperhidrosis frequency or severity for 3 months prior to enrollment; they may be included. Doses of these agents should not be altered during the course of the study. (d) Any topical treatment for hyperhidrosis, requiring a prescription, within 3 days of enrollment. Anticholinergic agents [with the exception of sofpironium bromide] used to treat conditions such as, but not limited to, hyperhidrosis, asthma, incontinence, gastrointestinal cramps, and muscular spasms by any route of administration (e.g., IV, oral, inhaled, topical) within 30 days of the enrollment. Use of potent oral inhibitors of cytochrome P450 CYP3A & CYP2D6 and transporter inhibitors (OCT2/MATE1/MATE2) 14 days prior to enrollment. The use of topical antifungal medications is permitted if not applied in the treatment area. Any oral or topical homeopathic or herbal treatment (i.e., alternative therapies such as sage tablets, chamomile, valerian root and St. John's Wort) within 14 days of enrollment. Use of any cholinergic drug (e.g., bethanechol) within 30 days of enrollment. Use of any anti-anxiety and/or anti-depressant, amphetamine product or drugs with known anticholinergic side effects is prohibited with the following exceptions: (a) If a subject has been on a stable dose of an anti-anxiety and/or anti-depressant drug and has not had a recent change in hyperhidrosis frequency or severity for 3 months; they may be included. (b) An amphetamine product may be allowed if the dose has been stable for greater than or equal to 6 months without change in hyperhidrosis frequency or severity for 3 months. (c) Drugs with known anticholinergic side effects (taken within the last 30 days), including dry mouth, blurred vision, may be allowed based on the Principal Investigator's assessment. Known causes 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 hyperhidrosis symptoms initiated or exacerbated with menopause. Subjects with unstable type 1 or type 2 diabetes mellitus or thyroid disease, history of renal impairment, hepatic impairment, malignancy, glaucoma, intestinal obstructive or motility disease, obstructive uropathy, myasthenia gravis, benign prostatic hyperplasia (BPH), neurological conditions, psychiatric conditions, Sjögren's syndrome, Sicca syndrome, or cardiac abnormalities that may alter normal sweat production or may be exacerbated by the use of anticholinergics in the Investigator's opinion. 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. Unable or unwilling to undergo multiple venipunctures.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gel, 15%<br>Sofpironium Bromide Gel, 15%, applied once daily to each axilla for 24 weeks | Drug: Sofpironium Bromide Gel, 15%<br>* Sofpironium Bromide Gel, 15%<br>* Other names: BBI-4000;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Treatment Emergent Adverse Events (All TEAEs). | Summarized by MedDRA LLT with a 3 point severity scale of mild, moderate and severe. | Through study completion (24 weeks). | 
| The Number of Participants With Dermal Tolerability Symptoms of Burning, Stinging, Itching, Scaling or Erythema to the Axillae. | Summary of local site tolerability by maximum severity symptom rating on a 5-point scale (0=absent, 1=minimal, 2=mild,-3=moderate, 4=severe)-Safety Population | Through study completion (24 weeks). | 
| The Systemic Exposure (Ctrough) of Sofpironium and Its Primary Metabolite (BBI-4010) | Trough levels of sofpironium based on sampling schedule. | Through study completion (24 weeks). |