Drug Trials Snapshots: SOFDRA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the SOFDRA Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
SOFDRA (sofpironium bromide)
sof' drah
Botanix SB Inc.
Original Approval date: June 18, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
SOFDRA is an anticholinergic antiperspirant approved for primary axillary hyperhidrosis in adult and pediatric patients 9 years of age and older.
How is this drug used?
SOFDRA is a topical gel that is applied once daily, at bedtime.
Who participated in the clinical trials?
The FDA approved SOFDRA based on evidence from two clinical trials of 701 patients with primary axillary hyperhidrosis. The trials were conducted at 68 sites, all of which were in the United States. Both trials were used to assess efficacy and safety.
How were the trials designed?
SOFDRA was evaluated in two clinical trials of 701 patients 10 years of age or older with primary axillary hyperhidrosis. Both trials were randomized, multicenter, and vehicle-controlled.
Subjects were randomized to receive either SOFDRA or vehicle applied once daily at bedtime to each axilla (underarm). The co-primary endpoints were the proportion of subjects having at least a 2-point improvement in the Hyperhidrosis Disease Severity Measure-Axillary, 7-item (HDSM-Ax-7) scale score from Baseline to Day 43, and the change in gravimetric sweat production (GSP) from Baseline to Day 43.
How were the trials designed?
SOFDRA was evaluated in two trials: CARDIGAN 1 and CARDIGAN 2. Both trials were randomized, multicenter, and vehicle-controlled. The trials enrolled subjects 10 years of age or older with symptoms of axillary hyperhidrosis for at least six months’ duration, who produced at least 50 mg of sweat in each underarm with a combined total of at least 150 mg over a 5-minute period, and who had a HDSM-Ax-7 score ≥3. Subjects 12 years of age and older were asked to rate their underarm sweating severity and frequency since waking on the previous day (“since you woke up yesterday”) on the 11-item Hyperhidrosis Disease Severity Measure-Axillary Adult version instrument. The HDSM-Ax-7 scale score was calculated by taking an average of seven items, where the scale score ranges from 0 to 4 with a higher score representing greater underarm sweating severity.
Subjects were randomized to receive either SOFDRA or vehicle applied once daily at bedtime to each axilla. The co-primary endpoints were the proportion of subjects having at least a 2-point improvement in the HDSM-Ax-7 scale score from Baseline to Day 43, and the change in GSP from Baseline to Day 43.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of SOFDRA.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of SOFDRA.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of SOFDRA.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of SOFDRA.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics of Efficacy Trials
| Demographic | CARDIGAN 1 | CARDIGAN 2 | ||
| SOFDRA N=173 n(%) |
Vehicle N=177 n(%) |
SOFDRA N=180 n(%) |
Vehicle N=171 n(%) |
|
| Age group, years | ||||
| 9 to <12 | 1 (1) | 0 (0) | 2 (1) | 2 (1) |
| 12 to <18 | 14 (8) | 12 (7) | 13 (7) | 8 (5) |
| 18 to <65 | 158 (91) | 163 (92) | 161 (89) | 158 (92) |
| ≥65 | 0 (0) | 2 (1) | 4 (2) | 3 (2) |
| Sex | ||||
| Female | 98 (57) | 99 (56) | 92 (51) | 103 (60) |
| Male | 75 (43) | 78 (44) | 88 (49) | 68 (40) |
| Race | ||||
| American Indian or Alaska Native | 0 (0) | 0 (0) | 2 (1) | 1 (1) |
| Asian | 1 (1) | 3 (2) | 4 (2) | 1 (1) |
| Black or African American | 31 (18) | 43 (24) | 32 (18) | 34 (20) |
| White | 140 (81) | 130 (73) | 141 (78) | 133 (78) |
| Unknown or not reported | 1 (1) | 1 (1) | 1 (1) | 2 (1) |
| Ethnicity | ||||
| Hispanic or Latino | 61 (35) | 60 (34) | 48 (27) | 45 (26) |
| Not Hispanic or Latino | 111 (64) | 117 (66) | 132 (73) | 124 (73) |
| Not reported | 1 (1) | 0 (0) | 0 (0) | 2 (1) |
Source: Adapted from FDA Review
What are the benefits of this drug?
More subjects on SOFDRA had at least a 2-point improvement in the HDSM-Ax-7 scale score from Baseline to Day 43 than subjects on vehicle. The HDSM-Ax-7 scale rates underarm sweating severity and frequency since waking on the previous day. The endpoint was evaluated in subjects 12 years of age and older.
Subjects treated with SOFDRA had a greater reduction in GSP from Baseline to Day 43 than subjects treated with vehicle, where GSP was collected over a 5-minute period.
What are the benefits of this drug (results of trials used to assess efficacy)?
The co-primary endpoints were the proportion of subjects having at least a 2-point improvement in the HDSM-Ax-7 scale score from Baseline to Day 43 and the change in GSP from Baseline to Day 43. At Baseline, all subjects were to produce at least 50 mg of sweat in each underarm with a combined total of at least 150 mg over a 5-minute period and have HDSM-Ax7 ≥3. The HDSM-Ax7 endpoint was evaluated in subjects 12 years of age and older.
Table 2. Efficacy Results, Efficacy Population
| Efficacy Endpoint | CARDIGAN 1 | CARDIGAN 2 | ||
| SOFDRA | Vehicle | SOFDRA | Vehicle | |
| HDSM Ax-7 (subjects ≥12 years) | N=172 | N=172 | N=178 | N=169 |
| ≥2 point improvement from Baseline to Day 43, % | 49 | 29 | 64 | 48 |
| Treatment difference, % (95% CI) | 18 (8, 29) | 17 (6, 27) | ||
| GSP, mg/5 minutes (subjects ≥10 years) | N=173 | N=177 | N=180 | N=171 |
| Median Baseline | 214 | 229 | 208 | 231 |
| Median change from Baseline to Day 43 (Q1, Q3) | -128 (-201, -52) | -100 (-228, -29) | -143 (-260, -75) | -134 (-230, -60) |
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; GSP, gravimetric sweat production; HDSM-Ax-7, Hyperhidrosis Disease Severity Measure-Axillary, 7-item score; Q1, first quartile; Q3, third quartile
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: SOFDRA worked similarly in males and females.
- Race: SOFDRA worked similarly in White and Black or African American patients. The number of patients of other races was small; therefore, differences in how SOFDRA worked among other races could not be determined.
- Age: SOFDRA worked similarly in patients younger and older than 18 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 and Table 4 summarize the efficacy results by subgroup for the combined trials (CARDIGAN 1 and CARDIGAN 2).
Table 3. Percentage of Subjects With ≥2 Point Improvement in the HDSM-Ax-7 Scale Score From Baseline to Day 43 in Subjects ≥12 Years (CARDIGAN 1 and CARDIGAN 2 Combined)
| Subgroup | SOFDRA N=350 % |
Vehicle N=346 % |
Difference % (95% CI) |
| Age group, years, (n1, n2)a | |||
| 12 to <18 (27, 20) | 55 | 33 | 23 (-6, 52) |
| ≥18 (323, 326) | 57 | 40 | 17 (10, 25) |
| Sex, (n1, n2) | |||
| Female (188, 201) | 62 | 39 | 23 (13, 33) |
| Male (162, 145) | 51 | 40 | 11 (0.2, 23) |
| Race, (n1, n2) | |||
| Black or African American (61, 76) | 51 | 34 | 17 (1, 34) |
| White (280, 262) | 59 | 42 | 17 (9, 26) |
| Other races (9, 8)b | 33 | 13 | 21 (NA, NA) |
| Ethnicityc, (n1, n2) | |||
| Hispanic or Latino (108, 104) | 55 | 43 | 12 (-1, 26) |
| Not Hispanic or Latino (241, 240) | 58 | 38 | 20 (11, 29) |
Source: Adapted from FDA Review
a (n1, n2) represents the sample size for SOFDRA and vehicle, respectively.
b Other races include: Asian, American Indian or Alaska Native, and unknown or not reported
c There were 3 subjects who did not report ethnicity: 1 subject in the SOFDRA arm and 2 subjects in the vehicle arm
Abbreviations: CI, confidence interval; HDSM-Ax-7, Hyperhidrosis Disease Severity Measure-Axillary, 7-item score; NA, not applicable
Table 4. Median Change in Gravimetric Sweat Production by Demographic Subgroups (CARDIGAN 1 and CARDIGAN 2 Combined)
| Subgroup | SOFDRA N=353 Median (Q1, Q3) |
Vehicle N=348 Median (Q1, Q3) |
| Age group, years, (n1, n2)a | ||
| 10 to 17 (30, 22) | -140 (-266, -59) | -92 (-142, -23) |
| ≥18 (323, 326) | -132 (-219, -68) | -126 (-231, -48) |
| Sex, (n1, n2) | ||
| Female (190, 202) | -123 (-205, -68) | -133 (-245, -52) |
| Male (163, 146) | -145 (-250, -65) | -104 (-205, -35) |
| Race2, (n1, n2) | ||
| Black or African American (63, 77) | -136 (-224, -56) | -109 (-232, -10) |
| White (281, 263) | -132 (-216, -71) | -125 (-225, -53) |
| Other races (9, 8)b | -183 (-395, -63) | -143 (-221, -80) |
| Ethnicityc, (n1, n2) | ||
| Hispanic or Latino (109, 105) | -125 (-233, -58) | -112 (-232, -46) |
| Not Hispanic or Latino (243, 241) | -139 (-218, -71) | -123 (-224, -47) |
Adapted from FDA review
a (n1, n2) represents the sample size for SOFDRA and vehicle, respectively.
b Other races include: Asian, American Indian or Alaska Native, and unknown or not reported
c There were 3 subjects who did not report ethnicity: 1 subject in the SOFDRA arm and 2 subjects in the vehicle arm
Abbreviations: Q1, first quartile; Q3, third quartile
What are the possible side effects?
The common adverse reactions reported in greater than 2% of those treated with SOFDRA were dry mouth (14%), blurry vision (9%), mydriasis or dilated pupils (7%), and urinary retention (2%).
Use with caution with a history of urinary retention, or difficulty sweating. Avoid use in hot or very warm environments. If there is blurred vision, stop or avoid operating a motor vehicle or machinery until symptoms resolve.
What are the possible side effects (results of trials used to assess safety)?
SOFDRA is an anticholinergic drug which can result in certain side effects. Approximately 40% of subjects reported at least one adverse event during the clinical trials. Locally, the application site reactions may include pain, redness, dermatitis, itching, and irritation. Also, anticholinergic products applied topically can be absorbed, and cause distant side effects including dry mouth, blurred vision, dilated pupils, and urinary retention. The adverse events were not serious and reversible.
Table 5. Adverse Reactions Occurring in ≥2% of Subjects
| Adverse Reactions | SOFDRA N=353 n (%) |
Vehicle N=347 n (%) |
| Dry mouth | 51 (14) | 2 (0.6) |
| Vision blurred | 30 (9) | 1 (0.3) |
| Mydriasis | 23 (7) | 0 |
| Urinary retention | 8 (2) | 0 |
Source: SOFDRA Prescribing Information
Note: COVID-19 was observed in 8 (2%) SOFDRA and 2 (0.6%) vehicle subjects.
Table 6. Local Skin Reactions Reported in ≥2% of Subjects
| Local Skin Adverse Reactions | SOFDRA N=353 n (%) |
Vehicle N=347 n (%) |
| Pain | 29 (8) | 6 (2) |
| Erythema | 23 (7) | 1 (0.3) |
| Dermatitis | 21 (6) | 1 (0.3) |
| Pruritus | 16 (5) | 2 (0.6) |
| Irritation | 8 (2) | 1 (0.3) |
| Exfoliation | 2 | 1 (0.3) |
Source: SOFDRA Prescribing Information
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in SOFDRA side effects among races could not be determined.
- Age: The numbers of patients older than 65 years and younger than 12 years of age was small; therefore, differences in the occurrence of side effects between younger and older age groups could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 7. Overview of Side Effects by Subgroup in Pooled Trials (CARDIGAN 1 and CARDIGAN 2), Safety Population
| Characteristic | SOFDRA, N=353 | Vehicle, N=347 | |||||
| All Patients n (%) |
All Grades n/Ns (%) |
Grades 3 to 4 n/Ns (%) |
All Patients n (%) |
All Grades n/Ns (%) |
Grades 3 to 4 n/Ns (%) |
||
| Sex, n (%) | 190 (53.8) | 75/190 (39.5) | 5/190 (2.6) | 201 (57.9) | 26/201 (12.9) | 0/201 (0) | |
| Male | 163 (46.2) | 68/163 (41.7) | 4/163 (2.5) | 146 (42.1) | 20/146 (13.7) | 0/146 (0) | |
| Race, n (%) | |||||||
| American Indian or Alaska Native | 2 (0.6) | 0/2 (0) | 0/2 (0) | 1 (0.3) | 0/1 (0) | 0/1 (0) | |
| Asian | 5 (1.4) | 4/5 (80.0) | 0/5 (0) | 4 (1.2) | 0/4 (0) | 0/4 (0) | |
| Black or African American | 63 (17.8) | 19/63 (30.2) | 2/63 (3.2) | 77 (22.2) | 16/77 (20.8) | 0/77 (0) | |
| White | 281 (79.6) | 118/281 (42.0) | 7/281 (2.5) | 262 (75.5) | 30/262 (11.5) | 0/262 (0) | |
| Unknown or not reported | 2 (0.6) | 2/2 (100) | 0/2 (0) | 3 (0.9) | 0/3 (0) | 0/3 (0) | |
| Age group, years, n (%) | |||||||
| 9 to 12 | 6 (1.7) | 0/6 (0) | 0/6 (0) | 2 (0.6) | 1/2 (50.0) | 0/2 (0) | |
| 13 to 16 | 16 (4.5) | 5/16 (31.2) | 0/16 (0) | 13 (3.7) | 1/13 (7.7) | 0/13 (0) | |
| 17 to 30 | 147 (41.6) | 72/147 (49.0) | 3/147 (2.0) | 156 (45.0) | 20/156 (12.8) | 0/156 (0) | |
| ≥31 | 184 (52.1) | 66/184 (35.9) | 6/184 (3.3) | 176 (50.7) | 24/176 (13.6) | 0/176 (0) | |
| Ethnicity, n (%) | |||||||
| Hispanic or Latino | 109 (30.9) | 32/109 (29.4) | 1/109 (0.9) | 104 (30.0) | 12/104 (11.5) | 0/104 (0) | |
| Not Hispanic or Latino | 243 (68.8) | 110/243 (45.3) | 8/243 (3.3) | 241 (69.5) | 33/241 (13.7) | 0/241 (0) | |
| Not reported | 1 (0.3) | 1/1 (100) | 0/1 (0) | 2 (0.6) | 1/2 (50.0) | 0/2 (0) | |
Source: Adapted from FDA Review
Abbreviation: N, number of patients in the safety population; n, number of patients with given characteristic; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.