Poster presented at 13th Annual Winter Clinical Dermatology Conference | Maui, HI | January 12 - 17, 2018

Open-Label Study (ARIDO) Evaluating Long-Term Safety of Topical Glycopyrronium Tosylate (GT) in Patients With Primary Axillary Hyperhidrosis
Dee Anna Glaser,1 Adelaide A. Hebert,2 Alexander Nast,3 William P. Werschler,4 Stephen Shideler,5 Lawrence Green,6 Richard D. Mamelok,7 Janice Drew,8 John Quiring,9 David M. Pariser10
1Saint Louis University, St. Louis, MO; 2UTHealth McGovern Medical School, Houston, TX; 3Charité–Universitätsmedizin Berlin, Berlin, Germany; 4Premier Clinical Research, Spokane, WA; 5Shideler Dermatology and Skin Care Center, Carmel, IN; 6George Washington University School of Medicine, Washington, DC; 7Mamelok Consulting, Palo Alto, CA; 8Dermira, Inc., Menlo Park, CA; 
9QST Consultations, Allendale, MI; 10Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA

INTRODUCTION
• Hyperhidrosis affects an estimated 4.8% of the US population, or approximately 15.3 million people,1 and the

impact of hyperhidrosis on quality of life is reported as comparable to, or greater than, psoriasis or eczema2

• Glycopyrronium tosylate (GT; formerly DRM04) is a topical cholinergic receptor antagonist being developed for the
treatment of primary axillary hyperhidrosis in patients ≥9 years of age

• GT has been assessed in 2 replicate, randomized, double-blind, vehicle-controlled, pivotal phase 3 lead-in trials
(ATMOS-1 and ATMOS-2)

 – GT was generally well tolerated and demonstrated clinically meaningful improvements in disease severity and 
reductions in sweat production through 4 weeks in these trials3 

• ARIDO (NCT02553798) assessed the long-term safety of GT in a minimum of 100 patients with primary axillary
hyperhidrosis treated for at least 12 months

METHODS
Study Design
• ARIDO was a 44-week, open-label extension of ATMOS-1 (NCT02530281) and ATMOS-2 (NCT02530294) (Figure 1)

• In ATMOS-1/ATMOS-2 patients with primary axillary hyperhidrosis were randomized 2:1 to GT (3.75% topical
solution) or vehicle applied once daily to each axilla for 28 days (Figure 1)

• Patients who completed ATMOS-1/ATMOS-2 with ≥80% treatment compliance were eligible to continue into
ARIDO and receive open-label GT for up to 44 weeks or until early termination, including patients terminated once
the study objective of 100 patients receiving treatment for ≥12 months was achieved (Figure 1)

• Key inclusion criteria for ATMOS-1/ATMOS-2 were:

 – ≥9 years of age (patients <16 years were recruited only at US sites)

 – Primary axillary hyperhidrosis for ≥6 months

 – Gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla

 – Axillary Sweating Daily Diary (ASDD; for patients ≥16 years of age) or ASDD-Children (ASDD-C; for patients 
<16 years of age) axillary sweating severity item (Item 2) 4 score ≥4 (0 to 10 numeric rating scale)

 – Hyperhidrosis Disease Severity Scale (HDSS) ≥3

• Key exclusion criteria for ATMOS-1/ATMOS-2 were:

 – History of a condition that could cause secondary hyperhidrosis

 – Prior surgical procedure or treatment with a medical device for axillary hyperhidrosis

 – Treatment with iontophoresis within 4 weeks or treatment with botulinum toxin within 1 year for axillary hyperhidrosis

 – Axillary use of nonprescription antiperspirants within 1 week or prescription antiperspirants within 2 weeks

 – New or modified psychotherapeutic medication regimen within 2 weeks

 – Treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, 
or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change

 – Conditions that could be exacerbated by study medication

Figure 1.  Study Design

Wk 0
Randomization

BASELINEa
Wk 4 Wk 49

END
OF

STUDY

Screening Double-BlindTreatment
44-Week

Open-Label Extension

ARIDO
ATMOS-1

and
ATMOS-2

Target
Recruitment

(both trials
combined):
660 patients

randomized 2:1

GT

GT
564 (86.6%) patients continued into ARIDO

Vehicle

Wk 48

aBaseline for ARIDO was Week 0 of ATMOS-1/ATMOS-2
GT, topical glycopyrronium tosylate; Wk, week

Assessments
• Primary objective was long-term safety

 – Safety was evaluated via treatment-emergent adverse events (TEAEs) through Week 45 (Week 44 + 1 week 
safety follow-up), local skin reactions (LSRs) through Week 44, laboratory testing, vital signs, and physical 
examinations

 – TEAEs are summarized overall from the first application of study drug in ARIDO to Week 45

• Descriptive efficacy assessments evaluated in ARIDO were an extension of the primary endpoints in
ATMOS-1/ATMOS-2

 – Change from Baseline in ATMOS-1/ATMOS-2 in gravimetrically-measured sweat production at Week 44 
(up to 48 weeks of GT)

 – Change from Baseline in ATMOS-1/ATMOS-2 in HDSS responder rate (≥2-grade improvement) at Week 44 
(up to 48 weeks of GT)

• All safety and efficacy analyses were performed on the Safety Population (patients receiving ≥1 dose of GT and
having ≥1 post-Baseline assessment in ARIDO)

RESULTS
• The majority of patients (86.6%; N=564) completing ATMOS-1/ATMOS-2 (369 patients [65.4%] had received GT,

and 195 [34.6%] had received vehicle) continued into ARIDO (Figure 2)

• Of the patients enrolled in ARIDO, most patients were female (55.3%) and white (83.3%) with a mean age of 33.0
years and mean BMI of 27.3 kg/m2 (Table 1)

• The trial was terminated, per protocol, once study objectives were reached

 – A total of 226 patients completed 44 weeks of treatment

Figure 2.  Patient Disposition

GT
N=426

N=332 (58.9%)

GT
N=564a (86.6%)

N=226 (40.1%)

Vehicle
N=225

Completed 44 Weeks

Completed
ATMOS-1 and ATMOS-2N=651

GT
N=369

Vehicle
N=195

Entered ARIDO

Discontinued due to:
Lost to follow-up
Consent withdrawn
Adverse event
Noncompliance
Pregnancy
Protocol violation
Physician decision

(16.3%)
(14.5%)
(7.8%)
(1.4%)
(0.5%)
(0.4%)
(0.2%)

92
82
44

8
3
2
1

Discontinued due to:
Study objectives met/
study terminatedb 106 (18.8%)

a14 patients in ARIDO did not have a post-Baseline assessment and were therefore excluded from the Safety Population
bSponsor terminated study early, per protocol, when study objective of 100 patients receiving treatment for at least 12 months was achieved
GT, topical glycopyrronium tosylate

Table 1.  Demographics and Baselinea Disease Characteristics 
(Safety Populationb)

GT
(N=550)

Demographics
Age (years), mean ± SD 33.0 ± 11.4

Age group, n (%)
≥16 years 
<16 years

522 (94.9)
  28 (  5.1)

Female, n (%) 304 (55.3)

White, n (%) 458 (83.3)

BMI (kg/m2), mean ± SD 27.3 ± 5.0

Baseline Disease Characteristics
Sweat production (mg/5 min),

c
 mean ± SD 164.7 ± 145.0 

HDSS,d,e n (%)
Grade 3
Grade 4

348 (63.3)
201 (36.5)

Quality of Life
DLQI,f mean ± SD
CDLQI,g mean ± SD

11.4 ± 5.9
8.9 ± 5.4

aBaseline in ATMOS-1/ATMOS-2
bPatients receiving ≥1 dose of GT and having ≥1 post-Baseline assessment in ARIDO
cGravimetrically-measured average from the left and right axillae 
dHDSS ≥3 was an inclusion criteria
eN=549; 1 subject entered ATMOS-2 with HDSS=2, which was a protocol violation
fPatients >16 years of age
gPatients ≤16 years of age
BMI, body mass index; CDLQI, Children’s DLQI; DLQI, Dermatology Life Quality Index; GT, topical glycopyrronium tosylate; HDSS, Hyperhidrosis Disease Severity Scale; SD, standard deviation

Efficacy Assessments
• Through Week 44/ET in ARIDO (up to 48 weeks of GT), GT-treated patients continued to demonstrate

improvements in efficacy measures, including sweat production and HDSS responder rate (Figure 3)

 – From Baseline in ATMOS-1/ATMOS-2 to Week 44/ET in ARIDO, mean sweat production decreased by
95.7 ± 140.8 mg/5 min, which was maintained from a decrease of 107.6 ± 207.2 mg/5 min in GT-treated 
patients after 4 weeks in ATMOS-1/ATMOS-2 (Figure 3A)

 – At Week 44/ET in ARIDO, HDSS responder rate (≥2-grade improvement) was 63.2%, a further improvement 
from 59.1% in GT-treated patients at Week 4 in ATMOS-1/ATMOS-2

• HDSS grade improved by 1, 2, and 3 grades in 30.9%, 46.7%, and 16.5% of patients, respectively (Figure 3B)

Figure 3.  Mean Sweat Production and HDSS Improvement From 
Baselinea to Week 44/ET (Safety Populationb)

Baseline
(N=550)

164.7

Week 44/ET
(N=430)

63.1

Mean CfB: -95.7 ± 140.8

None

5.9%

1 Grade

30.9%

2 Grades

46.7%

3 Grades

16.5%

Improvement

350

300

250

200

150

100

50

-100

-50

0

M
ea

n 
S

w
ea

t P
ro

du
ct

io
n 

(m
g/

5 
m

in
)

A. Sweat Productionc
100

80

60

40

20

0

P
ro

po
rt

io
n 

of
 S

ub
je

ct
s 

(%
)

B. HDSS Improvementd

aBaseline in ATMOS-1/ATMOS-2
bPatients receiving ≥1 dose of GT and having ≥1 post-Baseline assessment in ARIDO
cGravimetrically-measured average from the left and right axillae 
dN=437
CfB, change from Baseline; ET, early termination; HDSS, Hyperhidrosis Disease Severity Scale

Safety Assessments
• After 44 weeks, 329 (59.8%) patients reported ≥1 TEAE, though most were mild or moderate in severity (Table 2)

• A total of 44 (8.0%) patients discontinued due to a TEAE and 7 (1.3%) reported ≥1 serious TEAE (Table 2)

• Prespecified anticholinergic TEAEs of interest were reported in 78 (14.2%) patients; most were mild or moderate
in severity and were able to be managed by dose interruption (Table 2)

 – 37 patients reported 45 vision blurred events; 40 (88.9%) were bilateral

 – 29 patients reported 37 mydriasis events; 31 (83.8%) were unilateral

• Generally, TEAEs, including TEAEs prespecified as anticholinergic TEAEs of interest, did not increase over time
with longer duration of exposure (Table 3)

• 179 (32.5%) of patients reported LSRs, which were typically mild or moderate in severity (Figure 4)

• There were no clinically meaningful changes in laboratory parameters or vital signs

Table 2.  Summary of Treatment-Emergent Adverse Events From 
Baselinea to Week 45/ET (Safety Populationb)

GT
(N=550)

Any TEAE, n (%) 329 (59.8)
Any Serious TEAE, n (%)     7 (  1.3)c

Discontinuation due to a TEAE, n (%)   44 ( 8.0)
Deaths, n (%) 0
Most frequently reported TEAEs (>5% patients), n (%)

Dry mouth
Vision blurred
Application site pain
Nasopharyngitis
Mydriasis

 93 (16.9)
 37 (  6.7)
 35 (  6.4)
 32 (  5.8)
 29 (  5.3)

Prespecified anticholinergic TEAEs of interest, n (%)
Vision blurred
Mydriasis
Urinary hesitation
Nocturia
Urine flow decreased
Hypermetropia
Pollakiuria
Pupils unequal

 78 (14.2) 
  37 (  6.7)d
  29 (  5.3)e
 23 (  4.2)
   2 (  0.4)
   2 (  0.4)
   1 (  0.2)
   1 (  0.2)
   1 (  0.2)

Any TEAEs
(N=329)

TEAEs by severity, n (%)
Mild
Moderate
Severe

148 (45.0)
153 (46.5)
  28 (  8.5)

Relation to study drug, n (%)
Not related
Related

131 (39.8)
198 (60.2)

Numbers in table represent the number of patients reporting ≥1 TEAE, not number of events 
aTEAEs are those with an onset after first application of study drug in ARIDO
bPatients receiving ≥1 dose of GT and having ≥1 post-Baseline assessment in ARIDO
cInfectious colitis, affective disorder, suicide attempt, mydriasis, chest pain, concussion, diverticulitis
d37 patients reported 45 vision blurred events; 40 (88.9%) were bilateral
e29 patients reported 37 mydriasis events; 31 (83.8%) were unilateral
ET, early termination; GT, topical glycopyrronium tosylate; TEAE, treatment-emergent adverse event

Table 3.  Summary of Frequently Reported TEAEs and TEAEs of Special 
Interest (Safety Populationa)

TEAEs, n (%)

Duration of Exposure

0 to 4
weeks

(N=550)

>4 to 8
weeks

(N=537)

>8 to 20 
weeks

(N=479)

>24 to 36 
weeks
(N=417)

>36 weeks
to ES

(N=365)

Any TEAE 176 (32.0) 148 (27.6) 102 (21.3) 78 (18.7) 59 (16.2)
TEAEs reported in >5% of 
patients

Dry mouth
Vision blurred
Application site pain
Nasopharyngitis
Mydriasis

  59 (10.7)
  11 (  2.0)
  16 (  2.9)
  14 (  2.5)
    8 (  1.5)

  23 (  4.3)
  14 (  2.6)
    9 (  1.7)
    9 (  1.7)
    8 (  1.5)

  19 (  4.0)
    7 (  1.5)
    5 (  1.0)
    4 (  0.8)
    9 (  1.9)

15 (  3.6)
  5 (  1.2)
  6 (  1.4)
  5 (  1.2)
  5 (  1.2)

  5 (  1.4)
  4 (  1.1)
  3 (  0.8)
  3 (  0.8)
   2 ( 0.5)

Prespecified 
anticholinergic TEAEs of 
interest

Vision blurred
Mydriasis
Urinary hesitation
Nocturia
Urine flow decreased
Hypermetropia
Pollakiuria
Pupils unequal

  11 (  2.0)
    8 (  1.5)
  14 (  2.5)
    2 (  0.4)
    1 (  0.2)

0
0

    1 (  0.2)

  14 (  2.6)
    8 (  1.5)
    4 (  0.7)

0
    1 (  0.2)

0
0
0

    7 (  1.5)
    9 (  1.9)
    4 (  0.8)

0
0
0
0
0

  5 (  1.2)
  5 (  1.2)
  2 (  0.5)

0
0

  1 (  0.2)
  1 (  0.2)

0

  4 (  1.1)
  2 (  0.5)
  1 (  0.3)

0
0
0
0
0

Numbers in table represent the number of patients reporting ≥1 TEAE, not number of events
TEAEs are those with an onset after first application of study drug in ARIDO
aPatients receiving ≥1 dose of GT and having ≥1 post Baseline assessment on ARIDO
ES, end of study; GT, topical glycopyrronium tosylate; TEAE, treatment-emergent adverse event

Figure 4.  Summary of Local Skin Reactions by Severity  From Baselinea 
to Week 44/ET (Safety Populationb)

Any
(N=179)

44 (25%)

120 (67%)

15 (8%)

Erythema
(N=116)

27 (23%)

81 (70%)

8 (7%)

Burning/Stinging
(N=73)

24 (33%)

42 (58%)

7 (10%)

Pruritus
(N=68)

26 (38%)

31 (46%)

11 (16%)

Dryness
(N=48)

8 (17%)

39 (81%)

1 (2%)

Edema
(N=34)

8 (24%)

24 (71%)

2 (6%)

Scaling
(N=25)

5 (20%)

20 (80%)

Mild
Moderate
Severe

200

160

120

80

40

0

N
um

be
r 

of
 L

S
R

s

Patients were counted as having an LSR if any post-Baseline assessment was mild, moderate, or severe
aBaseline in ATMOS-1/ATMOS-2
bPatients receiving ≥1 dose of GT and having ≥1 post-Baseline assessment in ARIDO
ET, early termination; GT, topical glycopyrronium tosylate; LSR, local skin reaction

CONCLUSIONS
• Safety results were consistent with anticholinergic treatment and with the

safety profile observed in prior GT studies,3 with no new or unexpected
findings

 – Most TEAEs were mild or moderate in severity and considered by the
Investigator to be related to study drug

 – A low number of subjects discontinued due to a TEAE
 – While approximately one-third of patients reported local skin reactions, most 

were mild or moderate in severity
 – Incidence of TEAEs, including prespecified anticholinergic TEAEs of 

interest, did not increase with long-term treatment
• Efficacy measures obtained at the end of treatment in ARIDO indicated that

subjects had maintained sweat production reduction and less bothersome
sweating compared with Baseline in ATMOS-1/ATMOS-2

• GT was generally well tolerated and improvements in efficacy measures were
maintained in patients with primary axillary hyperhidrosis when applied once
daily to both axillae over a maximum of 48 weeks

References
1. Doolittle et al. Arch Dermatol Res. 2016;308(10):743-9. 2. Hamm. Dermatol Clin. 2014;32(4):467-76. 3. Pariser et al. Poster presented
at: 25th European Academy of Dermatology and Venerology Congress; September 28-October 2, 2016; Vienna, Austria. 4. Glaser et al. 
Poster presented at: 13th Maui Derm for Dermatologists Congress; March 20-24, 2017; Maui, HI. 

Acknowledgements 
This study was funded by Dermira, Inc. Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL). 
All costs associated with development of this poster were funded by Dermira, Inc.

Author Disclosures
DAG: Consultant and investigator for Dermira, Inc. AAH: Consultant for Dermira, Inc.; employee of the University of Texas Medical School, 
Houston, which received compensation from Dermira, Inc. for study participation. AN: Employee of Charité – Universitätsmedizin Berlin, 
which received compensation from Dermira, Inc. for study participation. WPW: Consultant and investigator for Dermira, Inc. SS: Investigator 
for Dermira, Inc. LG: Consultant and investigator for Dermira, Inc.; investigator for Brickell. RDM: Consultant for Dermira, Inc. JD: Employee 
of Dermira, Inc. JQ: Employee of QST Consultations. DMP: Consultant and investigator for Dermira, Inc.