Poster presented at the 36th Fall Clinical Dermatology Conference | Las Vegas, NV | October 12-15, 2017

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

• Topical glycopyrronium tosylate (GT; formerly DRM04) is a 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 

• This 44-week, open-label extension study (ARIDO; NCT02553798) assessed 
the long-term safety of GT in patients with primary axillary hyperhidrosis 
who completed ATMOS-1 (NCT02530281; sites in the US and Germany) or 
ATMOS-2 (NCT02530294, sites in US only)

METHODS
Study Design
• ARIDO was a 44-week open-label extension of ATMOS-1/ATMOS-2, 4-week, 

double-blind, phase 3 clinical trials in which 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 44 weeks or to early termination (ET; Figure 1)

• Eligible patients were ≥9 years of age (patients <16 years were only 
recruited at US sites) and had primary axillary hyperhidrosis for ≥6 months, 
with 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), and 
Hyperhidrosis Disease Severity Scale (HDSS) ≥3

• Patients were excluded for 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; 
and/or 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-Blind

Treatment

44-Week

Open-Label Extension

ARIDO
ATMOS-1

and

ATMOS-2

Target

Recruitment:

330 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 Baseline in ATMOS-1/ATMOS-2 to 
Week 45 (up to 48 weeks of GT) and by duration of exposure to GT in both 
ATMOS-1/ATMOS-2 and ARIDO

• 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)

Figure 2.  Patient Disposition

GT

N=369

GT

N=564

N=226

(40.1%)

Vehicle

N=195

Eligible ATMOS-1/ATMOS-2

participants who entered ARIDO

(N=564)

Completed Week 44 

of ARIDO

Early Discontinuation

Lost to follow-up

Consent withdrawn

Adverse event

Noncompliance

Pregnancy

Protocol violation

Physician decision

232

92

82

44

8

3

2

1

Patients at 

<Week 44 When 

Study Objectives

Were Achieved
a

106

aStudy objectives were 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
e
a
n

 S
w

e
a
t
 P

r
o

d
u

c
t
io

n
 (

m
g

/5
m

in
)

A. Sweat Production
c

100

80

60

40

20

0

P
r
o

p
o

r
t
io

n
 o

f
 S

u
b

je
c

t
s
 (

%
)

B. HDSS Improvement
d

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 48 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 
aBaseline in ATMOS-1/-2
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 Population)a,b

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

aIn ATMOS-1/ATMOS-2 and ARIDO combined
bPatients receiving ≥1 dose of GT and having ≥1 post Baseline assessment on ARIDO
Numbers in table represent the number of patients reporting ≥ TEAE, not number of events 
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%)

Pruritis
(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
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 LSRs, 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 abstract 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.  


	FC17PosterGlaserOpenLabelStudyARIDO.pdf