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

• ClinicalTrials.gov Identifier: NCT03627468
• Recruitment Status: Completed
• First Posted: August 13, 2018
• Last Update Posted: October 8, 2020
• Sponsor: Brickell Biotech, Inc.
• Information provided by (Responsible Party): Brickell Biotech, Inc.

Study Description

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 long-term safety, tolerability, and efficacy of sofpironium bromide gel applied topically to subjects with axillary hyperhidrosis.

Condition or disease	Intervention/treatment	Phase
Primary Axillary Hyperhidrosis	Drug: Sofpironium Bromide Gel, 5%; Drug: Sofpironium Bromide Gel, 15%	Phase 3

Detailed Description:

This is a randomized, open-label, phase 3 long-term study designed to evaluate the safety, local tolerability 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 300 subjects, will be randomized to receive one of two sofpironium bromide gel concentrations.

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 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 17 scheduled visits to take place over a 52 week period.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-label, Phase 3 Long-term Safety Study of Topically Applied Sofpironium Bromide (BBI-4000) Gel, 5% and 15% in Subjects With Axillary Hyperhidrosis
• Actual Study Start Date: September 5, 2018
• Actual Primary Completion Date: January 27, 2020
• Actual Study Completion Date: January 27, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gel, 5%; Sofpironium Bromide Gel, 5%, q.d. for 48 weeks	Drug: Sofpironium Bromide Gel, 5%; Sofpironium Bromide Gel, 5%; Other Name: BBI-4000
Experimental: Gel, 15%; Sofpironium Bromide Gel, 15%, q.d. for 48 weeks	Drug: Sofpironium Bromide Gel, 15%; Sofpironium Bromide Gel, 15%; Other Name: BBI-4000

Outcome Measures

Primary Outcome Measures :

1. The number of participants with treatment emergent adverse events [ Time Frame: Through study completion (48 weeks) ]
   Summarized by MedDRA LLT with a 3 point severity scale of mild, moderate and severe
2. The number of participants with dermal tolerability symptoms of burning, stinging, itching, scaling or erythema to the axillae [ Time Frame: Through study completion (48 weeks) ]
   Symptoms rated on a 5-point scale (0=absent, 1=minimal, 2=mild,-3=moderate, 4=severe)

Secondary Outcome Measures :

1. Change in Hyperhidrosis Disease Severity Measure-Axillary score [ Time Frame: From baseline to each visit through study completion (48 weeks) ]
   Change in score from baseline to each visit (range 0 [better] - 4 [worse])
2. Change in Dermatology Life Quality Index-Axilla score [ Time Frame: From Baseline to weeks 2, 6, 24 and 48 ]
   Change in score from baseline to each visit (range 0 [better] - 30 [worse])

Other Outcome Measures:

1. Change in the Hyperhidrosis Quality of Life Index score [ Time Frame: From baseline to weeks 2 and 6 ]
   Change in score from baseline to specified visits (range 0 [better] to 36 [worse])

Eligibility Criteria

• Ages Eligible for Study: 9 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female subject ≥9 years of age in good general health.
• Diagnosis of primary axillary hyperhidrosis that meets all the following criteria: (a) HDSM-Ax of 3 - 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 Baseline Visit (Visit 2).

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 6 months of the Baseline Visit (Visit 2). (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 28 days of the Baseline Visit (Visit 2). However, if a subject has been on a stable dose (in the opinion of the PI) of any of these medications and has not had a recent change in hyperhidrosis frequency or severity for 3 months prior to the Baseline Visit; they may be included. Doses of these agents should not be altered during the course of the study. (d) Any topical treatment for hyperhidrosis, requiring a prescription, within 15 days of Baseline Visit (Visit 2).
• Anticholinergic agents used to treat conditions such as, but not limited to, hyperhidrosis, asthma, incontinence, gastrointestinal cramps, and muscular spasms by any route of administration (e.g., IV, oral, inhaled, topical) within 28 days of the Baseline Visit (Visit 2).
• Use of potent oral inhibitors of cytochrome P450 CYP3A & CYP2D6 and transporter inhibitors (OCT2/MATE1/MATE2) 14 days prior to the Baseline Visit (Visit 2). 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 7 days of the Baseline Visit (Visit 2).
• Use of any cholinergic drug (e.g., bethanechol) within 15 days of the Baseline Visit (Visit 2).
• 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. (c) Drugs with known anticholinergic side effects (taken within the last 28 days), including dry mouth, blurred vision, may be allowed based on the Principal Investigator's assessment.

NOTE: If anticholinergic side effect(s) are experienced on these medications prior to starting study medication; document the side effect(s) and severities in the source document and the eCRF. The doses of these agents should not be altered during the course of the study.

• 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.
• Participating in a study of or used an investigational drug or device within 28 days prior to the Baseline Visit (Visit 2).
• Any major illness within 28 days before the screening examination.
• Any other condition, including psychiatric illness (depression and/or anxiety) that would interfere with study participation and/or evaluation of study endpoints or laboratory abnormality that, in the opinion of the Investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study.
• History or presence of supraventricular tachycardia, ventricular arrhythmias, atrial fibrillation or atrial flutter.

Contacts and Locations

Locations

United States, Alabama

Coastal Clinical Research, Inc.

Mobile, Alabama, United States, 36608

United States, Arkansas

Northwest Arkansas Clinical Trials Center

Rogers, Arkansas, United States, 72758

United States, Florida

Center for Clinical and Cosmetic Research

Aventura, Florida, United States, 33180

Skin Care Research, Inc.

Boca Raton, Florida, United States, 33486

Baumann Cosmetic & Research Institute

Miami, Florida, United States, 33137

Tory Sullivan MD PA

North Miami Beach, Florida, United States, 33162

Research Institute of the Southeast, LLC

West Palm Beach, Florida, United States, 33401

United States, Michigan

Grekin Skin Institute

Warren, Michigan, United States, 48088

United States, Minnesota

Minnesota Clinical Study Center

Fridley, Minnesota, United States, 55432

United States, Tennessee

Tennessee Clinical Research Center

Nashville, Tennessee, United States, 37215

United States, Texas

J&S Studies, Inc.

College Station, Texas, United States, 77845

Austin Institute for Clinical Research

Pflugerville, Texas, United States, 78660

Sponsors and Collaborators

Brickell Biotech, Inc.

Investigators

• Study Director: Sanjeev Ahuja, MD; Brickell Biotech, Inc.

More Information

• Responsible Party: Brickell Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT03627468
• Other Study ID Numbers: BBI-4000-CL-303
• First Posted: August 13, 2018
• Last Update Posted: October 8, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hyperhidrosis; Sweat Gland Diseases; Skin Diseases; Bromides; Anticonvulsants