Axillary Hyperhidrosis
Conditions
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.
Interventions
DRUGSofpironium Bromide, 15%
Active
DRUGVehicle
Vehicle gel
Sponsors
Botanix Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subject ≥ 9 years of age. * Diagnosis of primary axillary hyperhidrosis that meets the following criteria: (a) symptoms of hyperhidrosis 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Vehicle Arm vs. Sofpironium Bromide Gel, 15%) With and Without an Observed ≥2-point Improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score From Baseline to End of Treatment | Total Trial Participation was approximately 11-15 weeks; outcome measure time frame: Baseline (and treatment start) through to end of treatment, taking approximately 6 weeks. | Change in score from baseline to end of treatment of 7 questions from the patient reported outcome assessment - Hyperhidrosis Disease Severity Measure-Axillary-7; each question had a 5-point response (range 0 \[better\] - 4 \[worse\]). Total scores were calculated by averaging the score of all items, resulting in an axillary hyperhidrosis symptom range of 0 (no sweating) to 4 (worst possible sweating). Improvement corresponded to a ≥2-point reduction of individual participant score from baseline to end of treatment (end of treatment \[6 weeks\] score minus baseline score). Treatment arms compared included vehicle and Sofpironium Bromide Gel, 15%. Counts of participants (per treatment arm) with and without an observed ≥2-point improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score from baseline to end of treatment were used as the outcome value(s). |
| Observed Change in Participant (Vehicle Arm vs SB Gel 15% Arm) Ranked Gravimetric Sweat Production From Baseline to End of Treatment | Total Trial Participation was approximately 11-15 weeks; outcome measure time frame: Baseline (and treatment start) through to end of treatment, taking approximately 6 weeks. | Individual gravimetric sweat production values were reported as the combined measured weight (mg) of axillary (right +left axillae) sweat production at each visit. Gravimetric sweat production values were rank-transformed. Baseline GSP was the median rank of GSP measurements obtained on Visit 2, Visit 3, and Visit 4. End of Treatment GSP was the median rank of GSP measurements obtained on Visit 10, Visit 11, and Visit 12. The difference in ranked GSP from baseline to end of treatment (ranked GSP at end of treatment \[6 weeks\] minus ranked GSP at baseline) was used as the outcome value. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Sofpironium bromide, 15% gel, once per day
Sofpironium Bromide, 15%: Active | 180 |
| Vehicle Vehicle gel, once per day
Vehicle: Vehicle gel | 171 |
| Total | 351 |
Baseline characteristics
| Characteristic | Active | Vehicle | Total |
|---|---|---|---|
| Age, Continuous | 32.1 years STANDARD_DEVIATION 12.22 | 31.7 years STANDARD_DEVIATION 11.13 | 31.9 years STANDARD_DEVIATION 11.67 |
| Age, Customized 13-16 Years | 9 Participants | 5 Participants | 14 Participants |
| Age, Customized 17-30 Years | 77 Participants | 83 Participants | 160 Participants |
| Age, Customized ≥31 Years | 90 Participants | 81 Participants | 171 Participants |
| Age, Customized 9-12 Years | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants | 45 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 124 Participants | 256 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 34 Participants | 66 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 141 Participants | 133 Participants | 274 Participants |
| Sex: Female, Male Female | 92 Participants | 103 Participants | 195 Participants |
| Sex: Female, Male Male | 88 Participants | 68 Participants | 156 Participants |
| Time since start of Axillary Hyperhidrosis symptoms | 202.58 Months STANDARD_DEVIATION 131.948 | 194.36 Months STANDARD_DEVIATION 117.303 | 198.47 Months STANDARD_DEVIATION 124.672 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 180 | 0 / 171 |
| other Total, other adverse events | 80 / 180 | 9 / 171 |
| serious Total, serious adverse events | 1 / 180 | 0 / 171 |
Outcome results
Primary
Number of Participants (Vehicle Arm vs. Sofpironium Bromide Gel, 15%) With and Without an Observed ≥2-point Improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score From Baseline to End of Treatment
Change in score from baseline to end of treatment of 7 questions from the patient reported outcome assessment - Hyperhidrosis Disease Severity Measure-Axillary-7; each question had a 5-point response (range 0 \[better\] - 4 \[worse\]). Total scores were calculated by averaging the score of all items, resulting in an axillary hyperhidrosis symptom range of 0 (no sweating) to 4 (worst possible sweating). Improvement corresponded to a ≥2-point reduction of individual participant score from baseline to end of treatment (end of treatment \[6 weeks\] score minus baseline score). Treatment arms compared included vehicle and Sofpironium Bromide Gel, 15%. Counts of participants (per treatment arm) with and without an observed ≥2-point improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score from baseline to end of treatment were used as the outcome value(s).
Time frame: Total Trial Participation was approximately 11-15 weeks; outcome measure time frame: Baseline (and treatment start) through to end of treatment, taking approximately 6 weeks.
Population: Intent-to-treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active | Number of Participants (Vehicle Arm vs. Sofpironium Bromide Gel, 15%) With and Without an Observed ≥2-point Improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score From Baseline to End of Treatment | Number of Participants YES Observed ≥2-point improvement | 108 Participants |
| Active | Number of Participants (Vehicle Arm vs. Sofpironium Bromide Gel, 15%) With and Without an Observed ≥2-point Improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score From Baseline to End of Treatment | Number of Participants NO Observed ≥2-point improvement | 54 Participants |
| Vehicle | Number of Participants (Vehicle Arm vs. Sofpironium Bromide Gel, 15%) With and Without an Observed ≥2-point Improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score From Baseline to End of Treatment | Number of Participants YES Observed ≥2-point improvement | 75 Participants |
| Vehicle | Number of Participants (Vehicle Arm vs. Sofpironium Bromide Gel, 15%) With and Without an Observed ≥2-point Improvement in Hyperhidrosis Disease Severity Measure-Axillary-7 Item Total Score From Baseline to End of Treatment | Number of Participants NO Observed ≥2-point improvement | 84 Participants |
p-value: 0.002995% CI: [1.27, 3.15]Regression, Logistic
Primary
Observed Change in Participant (Vehicle Arm vs SB Gel 15% Arm) Ranked Gravimetric Sweat Production From Baseline to End of Treatment
Individual gravimetric sweat production values were reported as the combined measured weight (mg) of axillary (right +left axillae) sweat production at each visit. Gravimetric sweat production values were rank-transformed. Baseline GSP was the median rank of GSP measurements obtained on Visit 2, Visit 3, and Visit 4. End of Treatment GSP was the median rank of GSP measurements obtained on Visit 10, Visit 11, and Visit 12. The difference in ranked GSP from baseline to end of treatment (ranked GSP at end of treatment \[6 weeks\] minus ranked GSP at baseline) was used as the outcome value.
Time frame: Total Trial Participation was approximately 11-15 weeks; outcome measure time frame: Baseline (and treatment start) through to end of treatment, taking approximately 6 weeks.
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Observed Change in Participant (Vehicle Arm vs SB Gel 15% Arm) Ranked Gravimetric Sweat Production From Baseline to End of Treatment | -29.85 milligrams | Standard Deviation 93.19 |
| Vehicle | Observed Change in Participant (Vehicle Arm vs SB Gel 15% Arm) Ranked Gravimetric Sweat Production From Baseline to End of Treatment | -7.22 milligrams | Standard Deviation 93.255 |
p-value: 0.029695% CI: [-41.37, -2.16]ANCOVA