Clinical trial NCT03627468: A Safety Study of BBI-4000 Gel in Patients With Axillary Hyperhidrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Axillary Hyperhidrosis
Lead sponsor: Botanix Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-08-13
Enrollment: 300
Sex: ALL
Minimum age (years): 9
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: The Number of Participants With Treatment Emergent Adverse Events Cumulative to Week 48 by Maximum Severity
timeFrame: All safety subjects, reaching week 48 or not
measure: Number of Participants With Post-baseline Local Tolerability Assessments Results by Treatment Group (Population: Safety)
timeFrame: All Safety Subject, Baseline-Through study completion (48 weeks) or Not
Secondary outcomes:
measure: The Number (%) of Subjects Achieving (-) ≥ 1point (Negative) Change (or Decrease) in the Hyperhidrosis Disease Severity Measure-Axillary 11-item (HDSM-Ax-11©) Score
timeFrame: From baseline to each visit through study completion (48 weeks)
measure: The Number (%) of Subjects Achieving (-) ≥ 1.5 Point (Negative) Change (or Decrease) in the Hyperhidrosis Disease Severity Measure-Axillary 11-item (HDSM-Ax-11©) Score
timeFrame: From baseline to each visit through study completion (48 weeks)
measure: The Number (%) of Subjects Achieving (-) ≥ 2 Point (Negative) Change (or Decrease) in the Hyperhidrosis Disease Severity Measure-Axillary 11-item (HDSM-Ax-11©) Score
timeFrame: From baseline to each visit through study completion (48 weeks)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: Rogers
country: United States
facility: Northwest Arkansas Clinical Trials Center
state: Arkansas
city: Aventura
country: United States
facility: Center for Clinical and Cosmetic Research
state: Florida
city: Boca Raton
country: United States
facility: Skin Care Research, Inc.
state: Florida
city: Miami
country: United States
facility: Baumann Cosmetic & Research Institute
state: Florida
city: North Miami Beach
country: United States
facility: Tory Sullivan MD PA
state: Florida
city: West Palm Beach
country: United States
facility: Research Institute of the Southeast, LLC
state: Florida
city: Warren
country: United States
facility: Grekin Skin Institute
state: Michigan
city: Fridley
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: College Station
country: United States
facility: J&S Studies, Inc.
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research
state: Texas
Study officials:
affiliation: Botanix Pharmaceuticals
name: Patricia Walker, MD PhD
role: STUDY_DIRECTOR
References: