Hyperhidrosis
Conditions
Brief summary
To assess the safety and efficacy of 3 doses of BBI-4000 and vehicle (4 treatment arms), when applied once a day for 4 weeks, 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. Participating subjects will apply BBI-4000 once a day for 4 weeks in their axillae. The 4 week treatment period will be followed by a 2 week follow-up period. Safety will be assessed through collection of vital signs, adverse events, local skin responses, hematology and serum chemistry laboratory testing and ECGs. Efficacy will be assessed using the Hyperhidrosis Disease Severity Scale (patient reported outcome) and through gravimetrically measured sweat production. PK blood samples will be taken from study subjects from selected centers.
Interventions
DRUGBBI-4000 Gel, 5%
BBI-4000 Gel, 5%
BBI-4000 Gel, 10%
BBI-4000 Gel, 15%
DRUGVehicle
Placebo, BBI-4000 Gel, 0%
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Primary axillary hyperhidrosis of at least 6 months's duration * Hyperhidrosis disease severity score of 3 or 4 at baseline * Gravimetric test at baseline indicating at least 50 mg of sweat production at rest in each axilla, in 5 minutes (room temperature) * Willing to refrain from using any other antiperspirant agent for the duration of the study. * Females of childbearing potential must agree to use a medically acceptable method of contraception while participating in the study.
Exclusion criteria
* Any skin or subcutaneous tissue conditions in the axilla or near the axillary area, other than hyperhidrosis. * Prior use of any prohibited medication(s) or procedure(s) within the specified timeframe, including: 1. Botulinum toxin to the axillary area within 1 year of the baseline visit. 2. Axillary iontophoresis within 12 weeks of baseline visit. 3. Axillary thermolysis, sympathectomy or surgical procedures of the axillary area at any time in the past. * Use of systemic and/or topical anticholinergic treatment within 30 days of the baseline visit. * Subjects with hyperhidrosis symptoms initiated or exacerbated with their menopause. * Subjects with history of diabetes mellitus, renal impairment, hepatic impairment, thyroid disease, 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. * Subjects with known hypersensitivity to glycopyrrolate, anticholinergics, or any of the components of the topical formulation. * Pregnant or lactating women. * Use of an investigational drug within 30 days prior to the baseline visit. * Prior treatment with the study drug in a previous trial. * Any major illness within 30 days before the screening examination. * Any other condition or laboratory abnormality that, in the judgment 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Baseline through Week 4 (Day 29) | Severity is scored with increasing scale, scores 1-4 where minimal severity is scored: 1=My sweating is never noticeable and never interferes with my daily activities and most severe score is: 4=My sweating is intolerable and always interferes with my daily activities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Baseline through Week 4 (Day 29) | Severity is scored with increasing scale, scores 1-4 where minimal severity is scored: 1=My sweating is never noticeable and never interferes with my daily activities and most severe score is: 4=My sweating is intolerable and always interferes with my daily activities |
| Absolute Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 (Day 29) | Baseline through Week 4 (Day 29) | Sweat production unit of measure was weight-based (mg); absolute change was calculated by adding the left and right axillae sweat weights and calculating absolute change by subtracting day 29 from baseline sweat weights |
| Percent Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 | Baseline through Week 4 (Day 29) | Randomized participants that provided samples for gravimetric sweat measures, baseline and day 29; Percent Change was calculated by dividing absolute change by baseline gravimetric measurement x 100% |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BBI-4000 Dose 1 Low concentration of BBI-4000
BBI-4000 Low Concentration: BBI-4000 Low Dose | 47 |
| BBI-4000 Dose 2 Middle concentration of BBI-4000
BBI-4000 Middle Concentration: BBI-4000 Middle Dose | 48 |
| BBI-4000 Dose 3 High concentration of BBI-4000
BBI-4000 High Concentration: BBI-4000 High Dose | 48 |
| Vehicle Vehicle (placebo)
Placebo: Vehicle | 46 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | BBI-4000 Dose 1 | BBI-4000 Dose 2 | BBI-4000 Dose 3 | Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.6 years STANDARD_DEVIATION 10.34 | 33.4 years STANDARD_DEVIATION 10.61 | 35.5 years STANDARD_DEVIATION 11.64 | 32.4 years STANDARD_DEVIATION 8.23 | 33.5 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 12 Participants | 11 Participants | 13 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 36 Participants | 37 Participants | 33 Participants | 140 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 | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 13 Participants | 9 Participants | 11 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 35 Participants | 34 Participants | 35 Participants | 32 Participants | 136 Participants |
| Sex: Female, Male Female | 24 Participants | 25 Participants | 27 Participants | 27 Participants | 103 Participants |
| Sex: Female, Male Male | 23 Participants | 23 Participants | 21 Participants | 19 Participants | 86 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 / 47 | 0 / 48 | 0 / 48 | 0 / 46 |
| other Total, other adverse events | 8 / 47 | 12 / 48 | 14 / 48 | 6 / 46 |
| serious Total, serious adverse events | 0 / 47 | 0 / 48 | 0 / 48 | 0 / 46 |
Outcome results
Primary
Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4
Severity is scored with increasing scale, scores 1-4 where minimal severity is scored: 1=My sweating is never noticeable and never interferes with my daily activities and most severe score is: 4=My sweating is intolerable and always interferes with my daily activities
Time frame: Baseline through Week 4 (Day 29)
Population: Randomized subjects with reported scores on Baseline and Day 29 (week 4), Count of participants includes number of participants who did not report at-least a 2-point decrease in score (NO) and number of participants who did report at-least a 2-point decrease in score (YES); proportions were calculated as percentages = (# of participants/total # of participants that provided baseline and day 29 HDSS scores) x 100%
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BBI-4000 Gel, 5% | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 35 Participants |
| BBI-4000 Gel, 5% | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 12 Participants |
| BBI-4000 Gel, 10% | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 10 Participants |
| BBI-4000 Gel, 10% | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 37 Participants |
| BBI-4000 Gel, 15% | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 29 Participants |
| BBI-4000 Gel, 15% | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 18 Participants |
| Vehicle | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 36 Participants |
| Vehicle | Proportion of Subjects Achieving at Least 2-point Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 5 Participants |
Secondary
Absolute Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 (Day 29)
Sweat production unit of measure was weight-based (mg); absolute change was calculated by adding the left and right axillae sweat weights and calculating absolute change by subtracting day 29 from baseline sweat weights
Time frame: Baseline through Week 4 (Day 29)
Population: Randomized participants that provided samples for gravimetric measured sweat production: baseline and day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BBI-4000 Gel, 5% | Absolute Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 (Day 29) | -183.1 mg | Standard Deviation 370.85 |
| BBI-4000 Gel, 10% | Absolute Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 (Day 29) | -56.4 mg | Standard Deviation 277.81 |
| BBI-4000 Gel, 15% | Absolute Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 (Day 29) | -171.9 mg | Standard Deviation 344.54 |
| Vehicle | Absolute Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 (Day 29) | -172.9 mg | Standard Deviation 315.89 |
Secondary
Percent Change in Gravimetrically Measured Sweat Production From Baseline to Week 4
Randomized participants that provided samples for gravimetric sweat measures, baseline and day 29; Percent Change was calculated by dividing absolute change by baseline gravimetric measurement x 100%
Time frame: Baseline through Week 4 (Day 29)
Population: Randomized participants that provided samples for gravimetric sweat measures, baseline and day 29;
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BBI-4000 Gel, 5% | Percent Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 | -31.9 percentage of change | Standard Deviation 84.95 |
| BBI-4000 Gel, 10% | Percent Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 | -15.7 percentage of change | Standard Deviation 115.03 |
| BBI-4000 Gel, 15% | Percent Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 | -35.7 percentage of change | Standard Deviation 65.48 |
| Vehicle | Percent Change in Gravimetrically Measured Sweat Production From Baseline to Week 4 | -41.7 percentage of change | Standard Deviation 40.73 |
Secondary
Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4
Severity is scored with increasing scale, scores 1-4 where minimal severity is scored: 1=My sweating is never noticeable and never interferes with my daily activities and most severe score is: 4=My sweating is intolerable and always interferes with my daily activities
Time frame: Baseline through Week 4 (Day 29)
Population: Randomized subjects with reported scores on Baseline and Day 29 (week 4), Count of participants includes number of participants who did not report at-least a 1-point decrease in score (NO) and number of participants who did report at-least a 1-point decrease in score (YES); proportions were calculated as percentages = (# of participants YES or NO/total # of participants that provided baseline and day 29 HDSS scores) x 100%
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BBI-4000 Gel, 5% | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 25 Participants |
| BBI-4000 Gel, 5% | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 22 Participants |
| BBI-4000 Gel, 10% | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 21 Participants |
| BBI-4000 Gel, 10% | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 26 Participants |
| BBI-4000 Gel, 15% | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 13 Participants |
| BBI-4000 Gel, 15% | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 34 Participants |
| Vehicle | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | No | 23 Participants |
| Vehicle | Proportion of Subjects Achieving at Least 1-point Improvement in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Week 4 | Yes | 18 Participants |