Hyperhidrosis
Conditions
Keywords
sweat gland disease, sweating, underarm
Brief summary
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
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.
Interventions
DRUGBBI-4000 gel, 5%
BBI-4000 gel, 5% applied once to each axilla daily
BBI-4000 gel, 10% applied once to each axilla daily
BBI-4000 gel, 15% applied once to each axilla daily
Placebo, applied once to each axilla daily
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
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Score From Baseline to End of Therapy | overall ~6 Weeks, as listed in description includes: Baseline-Visit 1, Visit 4 and End of Therapy Visit - Days 41, 42, 43. | 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 |
| Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Treatment initiation through end of treatment (~42 days) and subsequent safety f/u (~14 days following end of treatment) | Subjects reporting more than one adverse event are counted only once using the highest severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | 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 | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Vehicle (Placebo), administered to each axilla once daily | 57 |
| BBI-4000 Gel, 5% BBI-4000 gel, 5% administered to each axilla once daily | 57 |
| BBI-4000 Gel, 10% BBI-4000 gel, 10% administered to each axilla once daily | 57 |
| BBI-4000 Gel, 15% BBI-4000 gel, 15% administered to each axilla once daily | 54 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 8 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 | 1 |
| Overall Study | Protocol Noncompliance | 1 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Vehicle | BBI-4000 Gel, 5% | BBI-4000 Gel, 10% | BBI-4000 Gel, 15% | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 8.62 | 30.8 years STANDARD_DEVIATION 10.22 | 33.7 years STANDARD_DEVIATION 11.29 | 30.7 years STANDARD_DEVIATION 9.24 | 31.3 years STANDARD_DEVIATION 9.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 8 Participants | 12 Participants | 15 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 49 Participants | 45 Participants | 39 Participants | 177 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 4 Participants | 9 Participants | 10 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 41 Participants | 47 Participants | 44 Participants | 42 Participants | 174 Participants |
| Sex: Female, Male Female | 30 Participants | 25 Participants | 22 Participants | 25 Participants | 102 Participants |
| Sex: Female, Male Male | 27 Participants | 32 Participants | 35 Participants | 29 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 | 0 / 57 | 0 / 54 |
| other Total, other adverse events | 9 / 57 | 17 / 57 | 19 / 57 | 28 / 54 |
| serious Total, serious adverse events | 0 / 57 | 1 / 57 | 0 / 57 | 0 / 54 |
Outcome results
Primary
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
Time frame: overall ~6 Weeks, as listed in description includes: Baseline-Visit 1, Visit 4 and End of Therapy Visit - Days 41, 42, 43.
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change of Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Score From Baseline to End of Therapy | -1.30 score on a scale | Standard Deviation 0.136 |
| BBI-4000 Gel, 5% | Change of Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Score From Baseline to End of Therapy | -2.02 score on a scale | Standard Deviation 0.135 |
| BBI-4000 Gel, 10% | Change of Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Score From Baseline to End of Therapy | -2.09 score on a scale | Standard Deviation 0.137 |
| BBI-4000 Gel, 15% | Change of Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) Score From Baseline to End of Therapy | -2.10 score on a scale | Standard Deviation 0.143 |
Primary
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.
Time frame: Treatment initiation through end of treatment (~42 days) and subsequent safety f/u (~14 days following end of treatment)
Population: Number (%) of Subjects Reporting at Least One: TEAE n(%), Safety Population: Vehicle (N=57), BBI-4000 5% (N=57), BBI-4000 10% (N=57), BBI-4000 15% (N=54)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Mild | 7 Participants |
| Vehicle | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Severe | 0 Participants |
| Vehicle | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Moderate | 2 Participants |
| BBI-4000 Gel, 5% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Mild | 7 Participants |
| BBI-4000 Gel, 5% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Severe | 2 Participants |
| BBI-4000 Gel, 5% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Moderate | 8 Participants |
| BBI-4000 Gel, 10% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Moderate | 7 Participants |
| BBI-4000 Gel, 10% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Mild | 10 Participants |
| BBI-4000 Gel, 10% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Severe | 2 Participants |
| BBI-4000 Gel, 15% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Mild | 11 Participants |
| BBI-4000 Gel, 15% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Severe | 4 Participants |
| BBI-4000 Gel, 15% | Number (%) of Subjects Reporting at Least One Treatment Emergent Adverse Event by Severity | Moderate | 13 Participants |
Secondary
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.
Time frame: 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
Population: Overall number of participants analyzed includes those who were compliant with the protocol. Compliance with the protocol per visit at Visits 2-4 (Days -21 to -7), Baseline Visit (Day 1), and Days 8, 15, 22, 29, 36, 41, 42, 43, and 57, affected the number of participants analyzed at these timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Baseline | 259.53 Combined Axilla GSP (mg) | Standard Deviation 141.738 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 8 | 137.36 Combined Axilla GSP (mg) | Standard Deviation 144.104 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 15 | 131.50 Combined Axilla GSP (mg) | Standard Deviation 100.171 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 22 | 141.10 Combined Axilla GSP (mg) | Standard Deviation 153.886 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 29 | 114.12 Combined Axilla GSP (mg) | Standard Deviation 91.999 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 36 | 142.87 Combined Axilla GSP (mg) | Standard Deviation 156.561 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 41 | 116.61 Combined Axilla GSP (mg) | Standard Deviation 132.62 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 42 | 110.96 Combined Axilla GSP (mg) | Standard Deviation 161.59 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 43 | 159.13 Combined Axilla GSP (mg) | Standard Deviation 157.113 |
| Vehicle | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 57 | 163.43 Combined Axilla GSP (mg) | Standard Deviation 193.565 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 15 | 114.24 Combined Axilla GSP (mg) | Standard Deviation 175.195 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 43 | 139.65 Combined Axilla GSP (mg) | Standard Deviation 291.857 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 22 | 102.43 Combined Axilla GSP (mg) | Standard Deviation 213.006 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 29 | 106.06 Combined Axilla GSP (mg) | Standard Deviation 180.981 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 36 | 105.16 Combined Axilla GSP (mg) | Standard Deviation 200.641 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 41 | 119.00 Combined Axilla GSP (mg) | Standard Deviation 195.636 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 57 | 112.09 Combined Axilla GSP (mg) | Standard Deviation 181.185 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 42 | 95.09 Combined Axilla GSP (mg) | Standard Deviation 157.573 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Baseline | 282.41 Combined Axilla GSP (mg) | Standard Deviation 201.92 |
| BBI-4000 Gel, 5% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 8 | 124.94 Combined Axilla GSP (mg) | Standard Deviation 199.072 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 42 | 111.98 Combined Axilla GSP (mg) | Standard Deviation 140.927 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 41 | 117.85 Combined Axilla GSP (mg) | Standard Deviation 141.07 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 57 | 177.62 Combined Axilla GSP (mg) | Standard Deviation 242.634 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Baseline | 281.63 Combined Axilla GSP (mg) | Standard Deviation 211.542 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 22 | 112.34 Combined Axilla GSP (mg) | Standard Deviation 128.033 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 36 | 124.33 Combined Axilla GSP (mg) | Standard Deviation 147.519 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 43 | 105.03 Combined Axilla GSP (mg) | Standard Deviation 108.026 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 8 | 113.77 Combined Axilla GSP (mg) | Standard Deviation 119.233 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 29 | 168.13 Combined Axilla GSP (mg) | Standard Deviation 230.825 |
| BBI-4000 Gel, 10% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 15 | 114.07 Combined Axilla GSP (mg) | Standard Deviation 169.784 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 29 | 117.60 Combined Axilla GSP (mg) | Standard Deviation 135.284 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 42 | 88.62 Combined Axilla GSP (mg) | Standard Deviation 103.408 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 36 | 126.44 Combined Axilla GSP (mg) | Standard Deviation 231.723 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 57 | 135.76 Combined Axilla GSP (mg) | Standard Deviation 165.62 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 41 | 93.21 Combined Axilla GSP (mg) | Standard Deviation 131.063 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 8 | 118.49 Combined Axilla GSP (mg) | Standard Deviation 129.393 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 15 | 106.68 Combined Axilla GSP (mg) | Standard Deviation 121.225 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 22 | 90.48 Combined Axilla GSP (mg) | Standard Deviation 98.38 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Baseline | 316.39 Combined Axilla GSP (mg) | Standard Deviation 201.478 |
| BBI-4000 Gel, 15% | Average Gravimetrically Measured Sweat Production (GSP) Observed by Visit, Per Protocol Population | Day 43 | 117.34 Combined Axilla GSP (mg) | Standard Deviation 159.217 |