Hyperhidrosis
Conditions
Brief summary
To assess the safety and local tolerability of BBI-4000 15% gel compared with vehicle (placebo) when applied topically once daily in subjects with palmar hyperhidrosis.
Detailed description
This is a Multicenter, Randomized, Double Blind, Vehicle-Controlled Study to Evaluate the Safety and Local Tolerability of Topically Applied BBI-4000 (Sofpironium Bromide) 15% Gel in Subjects with Palmar Hyperhidrosis. Participating subjects will apply either BBI-4000 15% or vehicle gel topically to the palms of both hands once daily for 4 consecutive weeks. The 4 week treatment period will be followed by a 2 week follow-up period. Safety and tolerability will be assessed through collection of vital signs, adverse events, assessment of local skin responses, ECG, UPT and blood sampling. Efficacy will be assessed through gravimetric sweat assessments as well as through the Hyperhidrosis Disease Severity Scale (HDSS).
Interventions
DRUGBBI-4000, 15%
OTHERVehicle 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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of primary palmar hyperhidrosis * HDSS of 3 or 4 at baseline * Gravimetric test at baseline indicating at least 100 mg of sweat production at rest in each palm and a sum of at least 250 mg in both palms, in 5 minutes (room temperature) * Symptoms of at least 6 months' duration * 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 of the palms, other than hyperhidrosis * Prior use of any prohibited medication(s) or procedure(s) within specified timeframe for the treatment of palmar hyperhidrosis, including: 1. Botulinum toxin to the palmar area within 9 months of baseline visit 2. Iontophoresis within 30 days of baseline visit 3. Palmar thermolysis, sympathectomy or surgical procedures of the palmar area any time in the past 4. Serotonergic agonist within 30 days of baseline visit 5. Any topical prescription treatment for hyperhidrosis within 30 days of baseline visit 6. Any over-the-counter topical antiperspirant/deodorant within 7 days of baseline visit * Use of anticholinergic agents within 30 days of baseline visit * Any oral or topical homeopathic or herbal treatment within 30 days of baseline visit * Use of any cholinergic drug within 30 days of baseline visit * Use of any anti-anxiety and/or anti-depressant, amphetamine products or drugs with known anticholinergic side effects * Hyperhidrosis secondary to any known cause * Subjects with history of 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. * 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. * Any major illness within 30 days before the screening examination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events by Severity | Baseline visit-Day 42 End of Participation | Each subject counted only once. Severity was rated Mild, Moderate or Severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Baseline to Day 29 (End of Treatment) Visit | HDSS assessment included a progressive hyperhidrosis severity scale, in which participants would rate the severity of their palmar hyperhidrosis for the past week with one of the following: 1-My sweating is never noticeable and never interfered with my daily activities; 2-My sweating is tolerable but sometimes interferes with my daily activities; 3-My sweating is barely tolerable and frequently interferes with my daily activities; 4-My sweating is intolerable and always interferes with my daily activities |
| Absolute Change (Day 29 - Baseline) in Palmar Gravimetrically Measured Sweat Production (GMSP) (mg) by Treatment Arm. | Baseline-Day 29 Participation | Individual Right and left palm gravimetric measured sweat production results (mg) were combined per participant at Baseline and Day 29 time points. Mean averages of individual absolute GMSP changes (Day 29 Combined GMSP-Baseline Combined GMSP) were compared between the two treatment arms. |
| Comparison of Number Subjects Achieving a Minimum of 50% Reduction in Gravimetrically Measured Sweat Production Day 29-baseline Among Both Treatment Arms | Baseline through day 29 (End of Treatment) | Visit combined sweat production (mg) was calculated by combining individual right and left palm gravimetric sweat production results (mg) at Baseline and Day 29 time points. Resulting difference was calculated by: Day 29 Combined GMSP - Baseline Combined GMSP. Percent reduction in sweat production was calculated by: ((Resulting difference GMSP score (mg)) / Baseline GMSP score (mg) x 100). The number of subjects who achieved ≥ 50% reduction in sweat production (YES) were reported, along with the proportion=number of subjects who achieved ≥ 50% reduction in sweat production / total number of subjects providing baseline and day 29 results x 100. The number of subjects who achieved \< 50% reduction in sweat production (NO) were reported, along with the proportion=number of subjects who achieved \< 50% reduction in sweat production / total number of subjects providing baseline and day 29 results x 100. |
| The Percent Change (%) Day 29 Combined GMSP From Baseline Combined GMSP Gravimetrically Measured Sweat Production (GMSP) in Combined (Right and Left) Palms. | Baseline-Day 29 End of Treatment | Individual Right and left palm gravimetric sweat production (GMSP) results (mg) were combined per participant at Baseline and Day 29 time points. Mean averages of individual percent change were compared between the two treatment arms. Individual % Change vs. Baseline was determined by: \[(D29 Right palm GMSP + D29 Left palm GMSP)-(Baseline Right palm GMSP + Baseline Left palm GMSP)\]/(Baseline Right palm GMSP + Baseline Left palm GMSP)\] |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BBI-4000, 15% 15% BBI-4000 (sofpironium bromide) topical gel
BBI-4000, 15% | 25 |
| Vehicle Vehicle (placebo) gel
Vehicle gel | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Non-compliance with Protocol | 0 | 2 |
| Overall Study | Non-compliance with Study Drug | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Vehicle | Total | BBI-4000, 15% |
|---|---|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 28 | 31.1 years STANDARD_DEVIATION 30 | 31.7 years STANDARD_DEVIATION 30 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 10 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 40 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 8 Participants | 4 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 38 Participants | 17 Participants |
| Sex: Female, Male Female | 20 Participants | 41 Participants | 21 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 25 |
| other Total, other adverse events | 8 / 24 | 4 / 25 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 |
Outcome results
Primary
Number of Treatment Emergent Adverse Events by Severity
Each subject counted only once. Severity was rated Mild, Moderate or Severe.
Time frame: Baseline visit-Day 42 End of Participation
Population: Participants receiving applying at least one dose of investigational treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BBI-4000 Gel, 15% | Number of Treatment Emergent Adverse Events by Severity | Mild | 14 Number of Events by Severity |
| BBI-4000 Gel, 15% | Number of Treatment Emergent Adverse Events by Severity | Moderate | 3 Number of Events by Severity |
| BBI-4000 Gel, 15% | Number of Treatment Emergent Adverse Events by Severity | Severe | 0 Number of Events by Severity |
| Vehicle Gel (Placebo) | Number of Treatment Emergent Adverse Events by Severity | Mild | 4 Number of Events by Severity |
| Vehicle Gel (Placebo) | Number of Treatment Emergent Adverse Events by Severity | Moderate | 0 Number of Events by Severity |
| Vehicle Gel (Placebo) | Number of Treatment Emergent Adverse Events by Severity | Severe | 0 Number of Events by Severity |
Secondary
Absolute Change (Day 29 - Baseline) in Palmar Gravimetrically Measured Sweat Production (GMSP) (mg) by Treatment Arm.
Individual Right and left palm gravimetric measured sweat production results (mg) were combined per participant at Baseline and Day 29 time points. Mean averages of individual absolute GMSP changes (Day 29 Combined GMSP-Baseline Combined GMSP) were compared between the two treatment arms.
Time frame: Baseline-Day 29 Participation
Population: Randomized participants (to one of two treatment arms) who provided Gravimetrically Measured Sweat Production (GMSP) results (Right and Left Palms) Baseline and day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BBI-4000 Gel, 15% | Absolute Change (Day 29 - Baseline) in Palmar Gravimetrically Measured Sweat Production (GMSP) (mg) by Treatment Arm. | -91.38 mg | Standard Deviation 385.12 |
| Vehicle Gel (Placebo) | Absolute Change (Day 29 - Baseline) in Palmar Gravimetrically Measured Sweat Production (GMSP) (mg) by Treatment Arm. | -156.62 mg | Standard Deviation 367.69 |
Secondary
Comparison of Number Subjects Achieving a Minimum of 50% Reduction in Gravimetrically Measured Sweat Production Day 29-baseline Among Both Treatment Arms
Visit combined sweat production (mg) was calculated by combining individual right and left palm gravimetric sweat production results (mg) at Baseline and Day 29 time points. Resulting difference was calculated by: Day 29 Combined GMSP - Baseline Combined GMSP. Percent reduction in sweat production was calculated by: ((Resulting difference GMSP score (mg)) / Baseline GMSP score (mg) x 100). The number of subjects who achieved ≥ 50% reduction in sweat production (YES) were reported, along with the proportion=number of subjects who achieved ≥ 50% reduction in sweat production / total number of subjects providing baseline and day 29 results x 100. The number of subjects who achieved \< 50% reduction in sweat production (NO) were reported, along with the proportion=number of subjects who achieved \< 50% reduction in sweat production / total number of subjects providing baseline and day 29 results x 100.
Time frame: Baseline through day 29 (End of Treatment)
Population: Randomized participants completing baseline through day 29 (End of Treatment) activities. Note: For this analysis, number analyzed includes 22 (gel, 15%) and 23 (Placebo) participants, and 22 (gel, 15%) and 23 (Placebo) participants' % reduction in sweat production for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BBI-4000 Gel, 15% | Comparison of Number Subjects Achieving a Minimum of 50% Reduction in Gravimetrically Measured Sweat Production Day 29-baseline Among Both Treatment Arms | The number of subjects who achieved < 50% reduction in sweat production (NO) | 18 participants |
| BBI-4000 Gel, 15% | Comparison of Number Subjects Achieving a Minimum of 50% Reduction in Gravimetrically Measured Sweat Production Day 29-baseline Among Both Treatment Arms | The number of subjects who achieved ≥ 50% reduction in sweat production (YES) | 4 participants |
| Vehicle Gel (Placebo) | Comparison of Number Subjects Achieving a Minimum of 50% Reduction in Gravimetrically Measured Sweat Production Day 29-baseline Among Both Treatment Arms | The number of subjects who achieved < 50% reduction in sweat production (NO) | 18 participants |
| Vehicle Gel (Placebo) | Comparison of Number Subjects Achieving a Minimum of 50% Reduction in Gravimetrically Measured Sweat Production Day 29-baseline Among Both Treatment Arms | The number of subjects who achieved ≥ 50% reduction in sweat production (YES) | 5 participants |
Secondary
Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29
HDSS assessment included a progressive hyperhidrosis severity scale, in which participants would rate the severity of their palmar hyperhidrosis for the past week with one of the following: 1-My sweating is never noticeable and never interfered with my daily activities; 2-My sweating is tolerable but sometimes interferes with my daily activities; 3-My sweating is barely tolerable and frequently interferes with my daily activities; 4-My sweating is intolerable and always interferes with my daily activities
Time frame: Baseline to Day 29 (End of Treatment) Visit
Population: Randomized participants who provided HDSS scores: baseline and day 29
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BBI-4000 Gel, 15% | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 1-Point Decrease : No | 8 Participants |
| BBI-4000 Gel, 15% | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 1-Point Decrease : Yes | 14 Participants |
| BBI-4000 Gel, 15% | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 2-Point Decrease : No | 20 Participants |
| BBI-4000 Gel, 15% | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 2-Point Decrease : Yes | 2 Participants |
| Vehicle Gel (Placebo) | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 2-Point Decrease : Yes | 2 Participants |
| Vehicle Gel (Placebo) | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 1-Point Decrease : No | 6 Participants |
| Vehicle Gel (Placebo) | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 2-Point Decrease : No | 21 Participants |
| Vehicle Gel (Placebo) | Proportion of Randomized Subjects Achieving a 1-grade & 2-grade Decrease in Hyperhidrosis Disease Severity Scale (HDSS) From Baseline to Day 29 | Proportion of Subjects with at least 1-Point Decrease : Yes | 17 Participants |
Secondary
The Percent Change (%) Day 29 Combined GMSP From Baseline Combined GMSP Gravimetrically Measured Sweat Production (GMSP) in Combined (Right and Left) Palms.
Individual Right and left palm gravimetric sweat production (GMSP) results (mg) were combined per participant at Baseline and Day 29 time points. Mean averages of individual percent change were compared between the two treatment arms. Individual % Change vs. Baseline was determined by: \[(D29 Right palm GMSP + D29 Left palm GMSP)-(Baseline Right palm GMSP + Baseline Left palm GMSP)\]/(Baseline Right palm GMSP + Baseline Left palm GMSP)\]
Time frame: Baseline-Day 29 End of Treatment
Population: Participants applying at least one dose of investigational treatment to each palm and providing both right \& left palm GMSP results at baseline and day 29. Combined GMSP results were determined by adding GMSP Left Palm + GMSP Right Palm results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BBI-4000 Gel, 15% | The Percent Change (%) Day 29 Combined GMSP From Baseline Combined GMSP Gravimetrically Measured Sweat Production (GMSP) in Combined (Right and Left) Palms. | -10.56 percentage of change | Standard Deviation 52.61 |
| Vehicle Gel (Placebo) | The Percent Change (%) Day 29 Combined GMSP From Baseline Combined GMSP Gravimetrically Measured Sweat Production (GMSP) in Combined (Right and Left) Palms. | -15.76 percentage of change | Standard Deviation 45.05 |