ACKNOWLEDGEMENTS Study funded by Galderma Research & Development, SNC, and editorial/poster support provided by Galderma Laboratories, L.P.

RESULTS

Subject Disposition
• 190 subjects (95 subjects per group) were enrolled at 26 sites in the United States and

Canada and 171 (90%) completed the study (Table 1).
• Subjects were predominantly Caucasian (91.1%) and female (72.1%), with a mean

age of 49.5 y and a history of chronic rosacea >5 y (70%).
Efficacy
• At week 12 hour 3, the total combined active group receiving the combination of IVM

+ BR showed superior efficacy (IGA success 0/1) compared to vehicle (55.8% vs.
36.8%, P = .007; Figure 1A).

• An advantage for patients receiving BR from day 1 was observed, with the IVM+BR/12W 
subgroup showing superior efficacy (61.2% vs. 36.8%, P = .003) at the end of the
study and early onset compared to vehicle (Figure 1B).

• IGA change was statistically significant to vehicle in the IVM+BR/12W group from
week 4 onwards (22.4% at week 4; Figure 1B).

• At week 12, comparison of the effect of BR before and 3h after application showed
that, in the IVM+BR/12W subgroup, the success rate almost doubled (from 32.7%
to 61.2% at hour 0 and hour 3, respectively; Figure 1C).

• Improvements in the IVM+BR/12W and IVM+BR/8W subgroups compared to the
vehicle group were also observed for CEA (P < 0.015; Figure 2)

• After 12 weeks of treatment, 16.3% of subjects in the IVM+BR/12W group had 100%
reduction in inflammatory lesion count (P = .015 compared to vehicle; Figure 3).

• A trend towards higher efficacy was observed in the IVM+BR/12W compared to the
IVM+BR/8W subgroup for both outcomes, corroborating the additive effect of BR
when taken concomitantly with IVM treatment.

Subject Reported Outcomes
• The subject global improvement of rosacea rate of excellent and good improvement

was 77.7%, 66.7%, and 55.2% in the IVM+BR/12W, IVM+BR/8W, and vehicle
groups, respectively.

Safety
• Only 8 treatment-related AEs in 6 subjects (3.2%) were reported; none were serious

or severe.
• One related AE leading to discontinuation (allergic dermatitis on the chest) was

reported in the IVM+BR/8W group.
• Related worsening of rosacea was observed in similar frequency with 1 (2.2%) AE in

the active IVM+BR/8W group vs. 3 (2.1%) AEs in the vehicle group.

INTRODUCTION

• Rosacea is often characterized by persistent centrofacial erythema and recurrent
inflammatory lesions.

• Individually, ivermectin 1% (IVM) cream and brimonidine 0.33% (BR) gel have
been shown to be effective against papules/pustules and persistent facial erythema,
respectively, in multiple studies.1,2

• The maximal effect of BR on erythema is observable around 3 hours after application.
• The objective was to evaluate the efficacy, safety, and patient satisfaction of IVM

in combination with BR (IVM+BR) versus their respective vehicles in subjects with
moderate to severe rosacea.

METHODS

Study Design
• This multicenter, randomized, double-blind, vehicle-controlled, and parallel group

comparison study included subjects with moderate to severe rosacea (Investigator
Global Assessment [IGA] ≥3, scale 0-4), characterized by persistent diffuse moderate
to severe erythema (Clinician Erythema Assessment [CEA] ≥3, scale 0-4) and
inflammatory lesions (15-70 papules/pustules).

Treatments
• Subjects were randomized 1:1:2 into 2 active and 1 double-blind vehicle group.
• IVM + BR active treatment groups:

 - Once-daily IVM and once-daily BR for 12 weeks (IVM+BR/12W subgroup; n=49)
 - Once-daily IVM for 12 weeks and once-daily BR vehicle for 4 weeks followed by

once-daily BR for the remaining 8 weeks (IVM+BR/8W subgroup; n=46)
• Vehicle group:

 - Once-daily IVM vehicle and once-daily BR vehicle for 12 weeks (vehicle group, n=95).
• A daily skin care regimen of gentle cleanser, moisturizing lotion, and facial moisturizer

with SPF 15 sunscreen was recommended and provided according to established
guidelines.3,4

Efficacy and Safety Endpoints
• Primary endpoint of IGA success (0/1, clear/almost clear) on a 5-point scale at week

12, 3 hours after BR application.
• Secondary efficacy endpoints included IGA at each visit, CEA, 100% reduction in

inflammatory lesion count, and subject global improvement of rosacea.
• AEs were monitored throughout the study.
• There was no adjustment of the Type I error.

CONCURRENT ADMINISTRATION OF IVERMECTIN 1% CREAM WITH BRIMONIDINE 0.33% GEL IMPROVES EFFICACY AND TOLERABILITY IN THE TREATMENT OF MODERATE TO SEVERE ROSACEA
 Linda Stein Gold, MD1; Kim Papp, MD2; Charles Lynde, MD3; Edward Lain, MD4; Melinda Gooderham, MD5; Sandra Johnson, MD6; Nabil Kerrouche, MSc7; Gregor Schäfer, MD8

1Department of Dermatology, Henry Ford Medical Center, Detroit, MI, USA; 2K. Papp Clinical Research, Probity Medical Research, Waterloo, ON, Canada; 3Lynde Institute for Dermatology, Markham, ON, Canada; 4Austin Institute for Clinical Research, Pflugerville, TX;  
5SKiN Centre for Dermatology, Probity Medical Research and Queen’s University Peterborough, ON, Canada; 6Johnson Dermatology, Fort Smith, AR; 7Galderma R&D, Sophia Antipolis, France; 8Galderma International, Paris, France

SOO.P-RD105069-02

SUMMARY
• Simultaneous administration of IVM 1% cream with BR 0.33% gel demonstrated

superior efficacy compared to their respective vehicles for the treatment of
moderate to severe rosacea.

• Early introduction of BR (from day 1), along with a complete daily skin care
regimen, may exert additional efficacy benefit and accelerate treatment success
without impairing tolerability.

• The IVM + BR association was well tolerated, with less than 5% related AEs.
• This regimen is a promising option for the comprehensive management of this

complex disease.

REFERENCES
1. Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two

randomized, double-blind, vehicle-controlled pivotal studies.  J Drugs Dermatol. 2014;13:316-323.
2. Fowler J Jr, Jackson M, Moore A, et al. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of

moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies. J Drugs
Dermatol. 2013;12:650-656.

3. Del Rosso JQ. Understanding skin cleansers and moisturizers: the correlation of formulation science with the art of clinical use. J Cosmet
Dermatol. 2003;16:19-31.

4. Schaller M, Almeida L, Bewley A, et al. Rosacea treatment update: Recommendations from the global ROSacea COnsensus (ROSCO) panel.
Br J Dermatol. 2016;176:465-471.

Figure 1. Investigator Global Assessment Success (ITT-LOCF)

40.7
Success

15.1
29.3 29.5

25.6

39.0
45.5

29.1

24.4
20.527.9

7.3 4.5
2.3 0 0

0

10

20

30

40

50

60

70

80

90

100

Vehicles IVM + BR / 8 Weeks IVM + BR / 12 Weeks

0 = Clear

1 = Almost Clear

2 = Mild Erythema

3 = Moderate Erythema

4 = Severe Erythema

68.3*
Success

75.0*
Success

*P = .007

Pe
rc

en
t o

f S
ub

jec
ts

4.2

6.5

16.3

0

2

4

6

8

10

12

14

16

18

Vehicles IVM + BR / 8 Weeks IVM + BR / 12 Weeks

Pe
rc

en
t o

f S
ub

je
cts

 w
ith

 1
00

%
 R

ed
uc

tio
n

in
 In

fla
m

m
at

or
y L

es
io

n 
Co

un
t 

P  = .015

Figure 2. Clinician Erythema Assessment at Week 12/hour 3 (ITT-LOCF)

Figure 3. Percentage of Subjects with 100% Reduction in Inflammatory 
Lesion Count (ILC) at Hour 3 Week 12 (ITT-LOCF)

Almost Clear
Clear

2.1
(n = 2)

13.7
(n = 13)

34.7
(n = 33)

42.1
(n = 40)

0

10

20

30

40

50

60

Vehicles (IVM + BR) Total Active IVM + BR

36.8
(n = 35)

55.8*
(n = 53)

*P = .007

Pe
rce

nt
 o

f S
ub

je
cts

A) At Week 12/hour 3

4.1

22.4

42.9

61.2

4.3

13.0

30.4

50.0

5.3 9.5

24.2

36.8

0

10

20

30

40

50

60

70

Baseline Week 4 Week 8 Week 12

Pe
rce

nt
 o

f S
ub

je
cts

 A
ch

ie
vin

g 
IG

A 
Su

cce
ss

 (I
GA

 0
 o

r 1
) IVM+BR/12W (N = 46)

IVM+BR/8W (BR Vehicle)

Vehicle (n = 95)
IVM+BR/8W (BR Active)

P  = .003

P  = .02

P  = .04

(n = 49) 

B) Percent of Subjects Achieving Success with IVM+BR/12W, IVM+BR/8W, or Vehicle

4.3
10.9

8.2

16.3

23.9

39.1

24.5

44.9

0

10

20

30

40

50

60

70

IVM + BR / 8 Weeks
Hour 0

IVM + BR / 8 Weeks
Hour 3

IVM + BR / 12 Weeks
Hour 0

IVM + BR / 12 Weeks
Hour 3

IGA 0
IGA 1

Su
cc

es
s R

at
e (

Pe
rc

en
t o

f S
ub

jec
ts 

wi
th

 a
n 

IG
A 

of
 0

 o
r 1

)

28.3%

50.0%

32.7%

61.2%

C) At Week 12/hour 0 Versus Week 12/hour 3 (before versus after application of BR)

Active Group Vehicle Group
IVM+BR/8W IVM+BR/12W

Subjects, n (%) 46 (100) 49 (100) 95 (100)
Completed, n (%) 41 (89.1) 44 (89.8) 86 (90.5)
Discontinued, n (%) 5 (10.9) 5 (10.2) 9 (9.5)

Adverse event, possibly related 1 (2.2) 0 1 (1.1)
Subject’s request 4 (8.7) 1 (2.0) 3 (3.2)
Lost to follow-up 0 3 (6.1) 3 (3.2)
Other 0 1 (2.0) 2 (2.1)

Table 1. Subject Disposition


	FC17PosterGaldermaSteinGoldConcurrentAdministration.pdf